Liraglutide alleviates myocardial ischemia‒reperfusion injury in diabetic mice

Diabetic patients are prone to acute myocardial infarction. Although reperfusion therapy can preserve the viability of the myocardium, it also causes fatal ischemia‒reperfusion injury. Diabetes can exacerbate myocardial ischemia‒reperfusion injury, but the mechanism is unclear. We aimed to characterize the effects of liraglutide on the prevention of ischemia‒reperfusion injury and inadequate autophagy. Liraglutide reduced the myocardial infarction area and improved cardiac function in diabetic mice. We further demonstrated that liraglutide mediated these protective effects by activating AMPK/mTOR-mediated autophagy. Liraglutide markedly increased p-AMPK levels and the LC3 II/LC3 I ratio and reduced p-mTOR levels and p62 expression. Pharmacological inhibition of mTOR increased cell viability and autophagy levels in high glucose and H/R-treated H9C2 cells. Overall, our study reveals that liraglutide acts upstream of the AMPK/mTOR pathway to effectively counteract high glucose- and H/R-induced cell dysfunction by activating AMPK/mTOR-dependent autophagy, providing a basis for the clinical prevention and treatment of ischemia‒reperfusion in diabetes. Key findings•Liraglutide could improve myocardial ischemia‒reperfusion injury in diabetic mice by activating AMPK/mTOR signaling pathway. What is known and what is new?•Liraglutide alleviates myocardial ischemia‒reperfusion injury, and diabetes exacerbates ischemia‒reperfusion injury. This study revealed that liraglutide could reduce the myocardial infarction area and improve cardiac function, and activation of the AMPK/mTOR signaling pathway promotes autophagy, thereby alleviating diabetic ischemia‒reperfusion injury. What are the implications and what should change now?•These findings highlight the potential of liraglutide in the clinical prevention and treatment of ischemia‒reperfusion during diabetes and further improve patient prognosis and survival rate.