Under physiological conditions, insulin regulates nutrient supply by stimulating NO production and consequent vasodilation [24], but in T2DM, altered insulin metabolic signaling reduces insulin-mediated coronary endothelial nitric oxide synthase (eNOS) activity and NO production [25] that, associated with the altered cytoplasmic Ca2+ concentration, causes excessive coronary vasoconstriction. This evidence concerns the gene INS and type 2 diabetes mellitus.