INS and Hyperglycemia: mTOR can phosphorylate AGC family of protein kinases, regulating cell survival and proliferation.79 Chronic hyperglycemia activates mTORC1 and reduces mTORC2 activity157 in islet β cells, which leads to the translocation of FOXO1 to nucleus and less nuclear PDX1, resulting in reduced insulin synthesis and secretion and impaired β cell mass80,158 (Fig. 2e).