Incremental effect of liraglutide on traditional insulin injections in rats with type 2 diabetes mellitus by maintaining glycolipid metabolism and cardiovascular function

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia, damaged insulin secretion and insulin resistance with high morbidity and mortality. Liraglutide (liragl) and insulin are effective hypoglycemic agents used in T2DM treatment. The potential effect of liragl in combination with insulin on T2DM remains unclear. The aim of the current study was to explore effects of liragl combined with insulin on glycolipid metabolism and cardiovascular function in rats with diabetes. A diabetes model was established in Sprague Dawley rats exposed to a high calorie and high sugar diet in conjunction with intraperitoneal injections of streptozotocin. Results indicated that liragl or insulin used alone decreased glucose and elevated insulin and c-peptide levels. However, their combination revealed greater effects. A significant increase in high-density lipoprotein cholesterol levels along with a decrease in total cholesterol, triglycerides and low-density lipoprotein cholesterol were observed in liragl- and insulin-treated rats compared with STZ-induced diabetes rats. Furthermore, co-administration of liragl and insulin significantly decreased sterol regulatory element-binding protein 1 levels and increased adenosine 5'-monophosphate kinase-α1 and carnitine palmitoyltransferase 1 expression. Combining liragl with insulin reduced myocardial hypertrophy level and gaps between cardiomyocytes compared with liragl or insulin treatment alone. Caspase-3 expression was significantly decreased by combination treatment of liragl and insulin. Oxidative damage was significantly decreased by co-administration of liragl and insulin through enhancing superoxide dismutase expression and reducing malondialdehyde. Furthermore, combination of liragl and insulin significantly reduced myocardial enzyme expression, including myoglobin, creatine kinase-muscle/brain and cardiac troponin I. In summary, the current study demonstrated synergistic effects of liragl and insulin injections on a T2DM rat model by maintaining glycolipid metabolism and cardiovascular function.