Exenatide protects renal ischemia reperfusion injury in type 2 diabetes mellitus

Background: In view of the reported efficacy of glucagons-like peptide-1 (GLP-1) on ischemia reperfusion (I/R) injury, this study was designed to assess the effect of exenatide (GLP-1 receptor agonist) on renal I/R in type 2 diabetes mellitus (T2DM). Materials and Methods: T2DM in rats were induced by administration of nicotinamide (230 mg/kg, i.p.), 15 min prior to the single dose of streptozotocin (65 mg/kg, i.v.). In vivo renal I/R were performed in both T2DM and normal rats. Results: The lipid peroxidation, xanthine oxidase activity, and nitric oxide level in renal tissue were significantly increased after I/R in diabetic rats compared to I/R in normal rats. Antioxidant enzymes such as glutathione, superoxide dismutase, catalase, and glutathione peroxidase were significantly reduced after I/R in diabetic rats compared to normal rats. Exenatide treatment significantly normalized these biochemical parameters compared to diabetic I/R rats. Serums TNF-α level and myeloperoxidase activity in renal tissue and apoptosis were also significantly normalized after administration of exenatide. Furthermore, treatment with exenatide (10 mcg/kg) had preserved the normal morphology of the kidney compared to I/R performed in T2DM rats. Conclusion: In conclusion, exenatide protects exaggerated renal I/R injury in T2DM. These findings have major implication in the treatment of ischemic injury that prone to develop in T2DM.