Liraglutide restores late cardioprotective effects of remote preconditioning in diabetic rats via activation of hydrogen sulfide and nuclear factor erythroid 2-related factor 2 signaling pathway

PURPOSE: The present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1α) and hydrogen sulfide (H(2)S). METHODS: Streptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H(2)S and HIF-1α levels. RESULTS: In diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H(2)S and HIF-1α levels in remote preconditioning-subjected diabetic rats. CONCLUSIONS: Liraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H(2)S and HIF-1α.