scholarly journals Altered function of insulin receptor substrate-1–deficient mouse islets and cultured β-cell lines

1999 ◽  
Vol 104 (12) ◽  
pp. R69-R75 ◽  
Author(s):  
Rohit N. Kulkarni ◽  
Jonathon N. Winnay ◽  
Molly Daniels ◽  
Jens C. Brüning ◽  
Sarah N. Flier ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Cell Lines ◽  
Insulin Receptor Substrate ◽  
Deficient Mouse ◽  
Β Cell ◽  
Insulin Receptor Substrate 1 ◽  
Mouse Islets

scholarly journals Glucose Effects on Beta-Cell Growth and Survival Require Activation of Insulin Receptors and Insulin Receptor Substrate 2

2009 ◽  
Vol 29 (11) ◽  
pp. 3219-3228 ◽  
Author(s):  
Anke Assmann ◽  
Kohjiro Ueki ◽  
Jonathon N. Winnay ◽  
Takahashi Kadowaki ◽  
Rohit N. Kulkarni
Keyword(s):  
Insulin Receptor ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Insulin Signaling ◽  
Insulin Receptors ◽  
Insulin Signaling Pathway ◽  
Insulin Receptor Substrate ◽  
Β Cells ◽  
Β Cell ◽  
Growth And Survival

ABSTRACT Insulin and insulin-like growth factor I (IGF-I) are ubiquitous hormones that regulate growth and metabolism of most mammalian cells, including pancreatic β-cells. In addition to being an insulin secretagogue, glucose regulates proliferation and survival of β-cells. However, it is unclear whether the latter effects of glucose occur secondary to autocrine activation of insulin signaling proteins by secreted insulin. To examine this possibility we studied the effects of exogenous glucose or insulin in β-cell lines completely lacking either insulin receptors (βIRKO) or insulin receptor substrate 2 (βIRS2KO). Exogenous addition of either insulin or glucose activated proteins in the insulin signaling pathway in control β-cell lines with the effects of insulin peaking earlier than glucose. Insulin stimulation of βIRKO and βIRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase. Control β-cells exhibited low expression of IGF-1 receptors compared to compensatory upregulation in βIRKO cells. The signaling data support the slow growth and reduced DNA and protein synthesis in βIRKO and βIRS2KO cells in response to glucose stimulation. Together, these studies provide compelling evidence that the growth and survival effects of glucose on β-cells require activation of proteins in the insulin signaling pathway.

The Association between Maternal/Fetal Insulin Receptor Substrate 1 Gene Polymorphism rs1801278 and Gestational Diabetes Mellitus in a Chinese Population

2021 ◽  
pp. 1-8
Author(s):  
Lingling Wu ◽  
Changping Fang ◽  
Jun Zhang ◽  
Yanchou Ye ◽  
Haiyan Zhao
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gene Polymorphism ◽  
Gestational Diabetes Mellitus ◽  
Insulin Receptor ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Insulin Receptor Substrate ◽  
Single Center ◽  
Insulin Receptor Substrate 1

<b><i>Objectives:</i></b> Insulin receptor substrate 1 (IRS1) is a crucial factor in the insulin signaling pathway. IRS1 gene polymorphism rs1801278 in mothers has been reported to be associated with gestational diabetes mellitus (GDM). However, it is not clear whether IRS1 gene polymorphism rs1801278 in fetuses is associated with their mothers’ GDM morbidity. The purpose of this study is to analyze the association between maternal, fetal, or maternal/fetal <i>IRS1</i> gene polymorphism rs1801278 and GDM risk. <b><i>Design:</i></b> The study was a single-center, prospective cohort study. In total, 213 pairs of GDM mothers/fetuses and 191 pairs of control mothers/fetuses were included in this study. They were recruited after they underwent oral glucose tolerance test during 24–28 weeks of gestation and followed up until delivery. All participants received the conventional interventions (diet and exercise), and no special therapy except routine treatment. <b><i>Methods:</i></b> A total of 213 pairs of GDM mothers/fetuses and 191 pairs of normal blood glucose pregnant mothers/fetuses were ge­notyped using PCR and DNA sequencing from January 2015 to September 2016. Maternal/fetal <i>IRS1</i> gene polymorphism rs1801278 was analyzed and compared between 2 groups. <b><i>Results:</i></b> There were no significant differences in the frequency of individual mothers’ or fetuses’ <i>IRS1</i> rs1801278 polymorphisms between 2 groups; if both the mothers and fetuses carried A allele, significantly lower GDM morbidity was observed in the mothers. <b><i>Limitations:</i></b> The sample size was relatively small as a single-center study. <b><i>Conclusions:</i></b> Our study suggested that maternal/fetal rs1801278 polymorphism of <i>IRS1</i> is a modulating factor in GDM; both mothers/fetuses carrying the A allele of rs1801278 may protect the mothers against the development of GDM.

scholarly journals Gly972Arg Variant of Insulin Receptor Substrate 1 Gene and Colorectal Cancer Risk in Overweight/Obese Subjects

2016 ◽  
Vol 31 (1) ◽  
pp. 68-72 ◽  
Author(s):  
Touraj Mahmoudi ◽  
Keivan Majidzadeh-A ◽  
Khatoon Karimi ◽  
Hamid Farahani ◽  
Reza Dabiri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Insulin Receptor ◽  
Case Control Study ◽  
Insulin Receptor Substrate ◽  
Protective Effects ◽  
Insulin Receptor Substrate 1 ◽  
Pcr Rflp ◽  
Obese Subjects ◽  
Control Study

Background Given the major role of obesity and insulin resistance (IR) in colorectal cancer (CRC), we investigated whether genetic variants in ghrelin ( GHRL), resistin ( RETN) and insulin receptor substrate 1 ( IRS1) were associated with CRC risk. Methods This study was conducted as a case-control study, and 750 subjects, including 438 controls and 312 patients with CRC, were enrolled and genotyped using the PCR-RFLP method. Results No significant differences were observed for GHRL (rs696217), RETN (rs3745367) and IRS1 (rs1801278, Gly972Arg or G972R) gene variants between the cases and controls. However, the IRS1 G972R R allele compared with the G allele and the G972R RR+GR genotype compared with the GG genotype appeared to be markers of decreased CRC susceptibility in the overweight/obese subjects (p = 0.024; odds ratio [OR] = 0.42, 95% confidence interval [95% CI], 0.20-0.91; and p = 0.048; OR = 0.42, 95% CI, 0.17-0.99, respectively). Furthermore, the R allele and RR+GR genotype were also associated with decreased risks for obesity in the patients with CRC (p = 0.007; OR = 0.35, 95% CI, 0.15-0.77; and p = 0.015; OR = 0.35, 95% CI, 0.15-0.72, respectively). Conclusions In accordance with previous studies, our findings suggest that the IRS1 G972R R allele and RR+GR genotype have protective effects for CRC in overweight/obese patients and for obesity in patients with CRC. Nevertheless, further studies are required to confirm these findings.

scholarly journals Dynamic Functional Relay between Insulin Receptor Substrate 1 and 2 in Hepatic Insulin Signaling during Fasting and Feeding

2008 ◽  
Vol 8 (1) ◽  
pp. 49-64 ◽  
Author(s):  
Naoto Kubota ◽  
Tetsuya Kubota ◽  
Shinsuke Itoh ◽  
Hiroki Kumagai ◽  
Hideki Kozono ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Insulin Signaling ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1 ◽  
Hepatic Insulin Signaling
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