NOS3 and diabetes mellitus: Mechanisms implicated in differing ischemic tolerance in acute vs. chronic DM include shifts in PI3K/Akt [12, 94, 95] and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling [90], mitochondrial glucose oxidation and malate-aspartate shuttle function [92], and capillary density, vascular endothelial growth factor (VEGF) expression and endothelial nitric oxide synthase (eNOS) signaling [94].