Downregulation of insulin dependent glucose uptake pathway has often been reported in upstream signaling molecules such as insulin receptor substrate 1, phosphatidylinositol 3-kinase, and Akt phosphorylation (89) with little to no impact on GLUT4 content and GLUT4 translocation in population with insulin resistance and T2D (90). The gene discussed is IRS1; the disease is type 2 diabetes mellitus.