GLP-1 analog liraglutide protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats

•Diabetic rats were treated with subcutaneous injections of liraglutide for 4 weeks.•Administration of liraglutide did not affect plasma glucose levels in diabetic rats.•Liraglutide prevents steatosis, oxidative stress and apoptosis in diabetic hearts.•Liraglutide improved expressions of genes and proteins mediating lipid metabolisms.•Liraglutide may have a beneficial effect on the diabetic heart via the mechanisms.

ObjectiveAccumulating evidence has implicated that GLP-1 may have a beneficial effect on cardiovascular but the mechanism is not fully understood. Here we show that GLP-1 analog, liraglutide, inhibits cardiac steatosis, oxidative stress and apoptosis in streptozotocin (STZ)-induced type 1 diabetic rats, via activation of AMPK-Sirt1 pathway.MethodsDiabetic rats were treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Myocardial steatosis (detected by oil red O staining and myocardial triglyceride and diacylglycerol (DAG) contents assay), expression of protein kinase C (PKC), heart NAD(P)H oxidase activity, oxidative stress markers (8-hydroxy-2′-deoxyguanosine staining), apoptosis (TUNEL analysis) and genes that affect apoptosis and lipid metabolism were evaluated.ResultsAdministration of liraglutide did not affect plasma glucose and insulin levels or body weights in STZ-induced diabetic rats, but normalized myocardial steatosis, expression of PKC, NAD(P)H oxidase activity, oxidative stress markers and apoptosis, all of which were significantly increased in diabetic hearts. Additionally, expression of genes mediating lipid uptake, synthesis and oxidation were increased in the diabetic hearts, and these increases were all reduced by liraglutide. In addition, liraglutide increased expression of Sirt1 and phosphorylated AMPK in the diabetic hearts.ConclusionsLiraglutide may have a beneficial effect on cardiac steatosis, DAG-PKC-NAD(P)H pathway, oxidative stress and apoptosis via activation of AMPK-Sirt1 pathway, independently of a glucose-lowering effect.