Greatly elevated [Ca2+]i–induced by hyperglycemia and glucose-stimulated ATP production–also promotes AMPK activity to inhibit insulin secretion; this seems contradictory given that hyperglycemia promotes insulin secretion, and it was postulated to function as a self-regulatory feedback mechanism that prevents excessive insulin secretion and hypoglycemia (Leclerc and Rutter, 2004; Granot et al., 2009). This evidence concerns the gene INS and Hyperglycemia.