In this study, we have evaluated the roles of IRS-1 and IRS-2 in signaling to the phosphatidylinositol (PI) 3-kinase pathway in the ob/ob mouse, a model of the insulin resistance of obesity and non-insulin-dependent diabetes mellitus.
These data indicate that IRS-2 is not a major gene for early-onset autosomal dominant type 2 diabetes, although a role of mutations in the promoter region cannot be excluded at this time.
IRS-2-deficient mice display all characteristics of type 2 diabetes, suggesting that dysfunction of the IRS-2 gene may contribute to the pathogenesis of human type 2 diabetes (4).
We tested the hypothesis that a common non-conservative amino acid substitution of IRS-2 (G1057D) might interact with overweight in the pathogenesis of type 2 diabetes.
Considering their key role in both insulin action and insulin secretion, IRS-1 and IRS-2 molecules have been considered plausible candidate genes involved in the pathogenesis of Type 2 diabetes.
Thus, the variants in the coding part of the IRS-2 gene are unlikely to have a major role in the development of type 2 diabetes in Finnish or Chinese subjects.
To understand the transcriptional regulation and to investigate the pathological influence upon Type II (non-insulin-dependent) diabetes mellitus of insulin receptor substrate 2 ( IRS2), the 5' flanking region of the human IRS2 gene was cloned and screened in Japanese diabetic patients.
Polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, IRS-1 (Gly(972)Arg) and IRS-2 (Gly(1057)Asp), influence susceptibility to type 2 diabetes.
The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic beta cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes.
To clarify the role of IRS-2 on the development of type 2 diabetes and obesity in Pima Indians, and particularly to investigate whether the effects of the Gly1057Asp polymorphism on metabolism are mediated by obesity, molecular scanning of the gene for mutations was performed and interaction of the polymorphism with obesity was tested.
The common polymorphisms of the IGF-1R, IRS-1 and IRS-2 genes may modify the weight change response to a lifestyle intervention but not the conversion from IGT to Type 2 diabetes, whereas IGF-1R may also regulate the risk of developing Type 2 diabetes.
Gene expressions of insulin receptor (INSR), vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 (IRS-1), IRS-2, glucose transporter 4 (GLUT4), and enzymes of the glycolytic pathway were decreased at least 50% in T2DM than in controls.
The aim of this study was to investigate the association of Gly1057Asp polymorphism in insulin receptor substrate-2 (IRS-2) gene among patients with type 2 diabetes in well defined ethnic groups from Djerba Island in Southeastern Tunisia.
The G1057D polymorphism in the insulin receptor substrate-2 (IRS-2) gene has been reported to be associated with insulin resistance, obesity and type 2 diabetes.
Study on establishment of congenic strains and screening of characteristics in IRS-2 deficient mice to support translational research on type 2 diabetes.
Importantly, pharmacological activation of the A2bAR by injection of the A2bAR ligand BAY 60-6583 for four weeks post HFD restores IRS-2 levels, and ameliorates T2D.
The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years.
The Gly1057D polymorphism in the insulin receptor substrate-2 (IRS-2) gene has been reported to be associated with insulin resistance, obesity and type 2 diabetes; little is known about its possible association with gestational diabetes mellitus (GDM).