On the contrary, specific knockout of 3‐phosphoinositol dependent protein kinase 1 (PDK1),92 IRS2,93, 94 INSR,95 IGF1,96 or S6K1,97 can repress AKT198 signaling transduction, leading to the decreases in insulin content and secretion, β‐cell mass and proliferation, and glucose tolerance, and eventually facilitating the development of hyperglycemia and T2DM. This evidence concerns the gene INS and type 2 diabetes mellitus.