Increased myocardial substrate uptake contributes to the protection of ischemic preconditioning: role of insulin-dependent Akt and AMPK activation

Introduction Switched myocardial substrate uptake from fatty acids to carbohydrate has been proposed to resist ischemia/reperfusion injury. We hypothesised that altered myocardial substrate uptake during early reperfusion may contribute to IPC-afforded cardioprotection. Methods Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion (MI/R). IPC was achieved by two cycles of 5 min ischemia and 5 min reperfusion. Myocardial glucose and fatty acid (FA) uptake were assessed at the end of 1 h reperfusion by determining fluorodeoxyglucose uptake and fatty acid translocase (FAT)/CD36 translocation, respectively. Results IPC significantly improved cardiac functions, reduced myocardial infarction, apoptotic cell death and blood CK/LDH levels following MI/R (all p Conclusions IPC increased both glucose and FA uptake during early reperfusion to resist myocardial injury via insulin/PI3K-dependent Akt and AMPK activation. Therefore, augmenting insulin signaling may be a potential therapy to improve myocardial substrate uptake and restore the cardioprotection of IPC in the diabetic hearts.