PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 6405894-0 1983 Effect of metformin on insulin receptor binding and diabetic control. Metformin 10-19 insulin receptor Homo sapiens 23-39 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 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 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 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 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 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 < 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 < 0.001). Metformin 118-127 insulin receptor Homo sapiens 9-11 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 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 < 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 < 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 < 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 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 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 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 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 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 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 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 15135305-0 2004 Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Metformin 0-9 insulin receptor Homo sapiens 79-95 15135305-1 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