SIRT6 and Hypoglycemia: SIRT6 activity has also an effect on insulin signaling throughdownregulation of glucose transporters GLUT1 and GLUT4 and decreasedphosphorylation of AKT,93 an importantregulator of cellular glucose uptake.94 Mechanistically, SIRT6 is involved in the inactivation of AKT upstreamproteins, including the insulin receptor substrates IRS1/2.93 Therefore, the absence of SIRT6 sensitizes theorganism to insulin action, giving a complementary explanation toglycolytic gene suppression for the observed hypoglycemia in SIRT6-knockoutmice.