Association of Irs1 GLY971ARG Gene Polymorphism With Insulin Resistance in Iranian Newly Diagnosed Diabetic Adults

Abstract

Context. Insulin receptor substrate-1 (IRS-1) has an important role in insulin signaling and the common Gly971Arg polymorphism is related to type 2 diabetes (T2D). IRS-1 Gly971Arg polymorphism can modify tyrosine phosphorylation at a specific site of IRS-1 and may have a critical role in the development of insulin resistance (IR).Objective. The purpose of this study was to investigate the association between this polymorphism and IR in Iranian patients with newly-diagnosed type 2 diabetes.Design. The study was conducted on 114 individuals with newly-diagnosed T2D and 118 healthy matched controls, aged 20-80 years. Fasting blood glucose and insulin were measured by the enzymatic method and enzyme-linked immunosorbent assay, respectively. Insulin-resistance was calculated by homeostasis model assessment estimatedinsulin resistance (HOMA-IR). The gene polymorphism was examined by polymerase chain reaction-restriction fragment length polymorphism.Results. There are significant differences between IRS1 Gly971Arg polymorphism and studied individuals (P<0.0001). The findings showed that the risk of developing T2D in individuals who had R-alleles was 3.74 folds higher than those without R-alleles. However, IRS1 Gly971Arg polymorphism was not associated with high HOMA-IR, high BMI and familial history of diabetes.Conclusions. Even though there was not a significant relationship between IRS-1 G971R polymorphism with insulin resistance and high BMI, this polymorphism was correlated to newly-diagnosed diabetic patients. Thus, the evaluation of IRS-1 G971R polymorphism may be helpful for predicting T2D new cases.

The 2039 A/G FSH receptor gene polymorphism influences glucose metabolism in healthy men

“…Generally, tyrosine kinase receptors (e.g., insulin receptor or insulin-like growth factor receptor) are able to influence the FSHR signaling [ 19 – 21 ]. In this regard, the insulin receptor substrate 1, which represents a co-factors linked to tyrosine kinase receptors, seems to play a role in the pathogenesis of insulin resistance [ 22 , 23 ]. Interestingly, it has been described as the hub that links FSH signaling pathway and the tyrosine kinase receptor-dependent cascade [ 24 , 25 ]; thus relating FSHR to the insulin receptor.…”