IRS1 and type 2 diabetes mellitus: It induces insulin resistance by promoting IRS-1 serine phosphorylation (Ser307) to inhibit insulin receptor signaling and downregulating AKT1 phosphorylation at Thr308/Ser473, thereby impairing GLUT4 membrane translocation and skeletal muscle glucose uptake.[20–23] One of the core pathological characteristics of T2DM is the progressive decline in function and reduction in number of pancreatic beta cells.