Figure 1: Schematic of proposed mechanism of opioid conditioning or ischemic conditioning induced cardioprotection. Opioids conditioning or ischemic conditioning protects the heart against ischemia-reperfusion injury, which initiates through stimulation of G-protein coupled receptors by ligands, then activates multiple signaling cascades, especially protein kinase C (PKC), survivor activating factor enhancement (SAFE) and reperfusion injury salvage kinase (RISK) pathways, and ultimately attenuates ischemia-reperfusion injury, but these effects are abolished or compromised under diabetic condition.