PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 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 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 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 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 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 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 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 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 insulin receptor substrate 1 Homo sapiens 253-258 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 25891779-3 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 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 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 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 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 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 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 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 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 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 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 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 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 23133528-7 2012 Moreover, metformin treatment increased gene expression of PI3K, IRS1, MAP3K, AKT and PTEN more than >1.5 fold. Metformin 10-19 insulin receptor substrate 1 Homo sapiens 65-69 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 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 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 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 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 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 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 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 12511230-5 2003 Tyrosine phosphorylation of IR?, IRS1, and IRS2 was increased by 2.7 fold (P < 0.01), 6.8 fold (P < 0.01), and 2.3 fold (P <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 12511230-7 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 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