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). This evidence concerns the gene SLC2A4 and type 2 diabetes mellitus.