Sitagliptin alleviated myocardial remodeling of the left ventricle and improved cardiac diastolic dysfunction in diabetic rats

Abstract

Objective: Sitagliptin, a dipeptidyl peptidase IV (DPP-Ⅳ) inhibitor, has a biological role in improving the serum levels of glucagon-like peptide 1 (GLP-1). Hence, we sought to determine the effect of sitagliptin on myocardial inflammation, collagen metabolism, lipid content and myocardial apoptosis in diabetic rats. Materials and methods: The type 2 diabetic rat model was induced by low-dose streptozotocin and a high-fat diet. Characteristics of diabetic rats were evaluated by electrocardiography, echocardiography and blood analysis. Cardiac inflammation, fibrosis, cardiomyocyte density, lipid accumulation, and receptor-interacting protein kinase 3 (RIP3) level, related to apoptosis, were detected by histopathologic analysis, RT-PCR and western blot analysis to evaluate the effects of sitagliptin on myocardial remodeling of the left ventricle. Results: Diabetic rats showed myocardial hypertrophy or apoptosis, inflammation, lipid accumulation, myocardial fibrosis, elevated collagen content, RIP3 overexpression, and left-ventricular dysfunction. Sitagliptin could reverse the overexpression of RIP3 and alleviate cellular apoptosis in myocardial tissues. It could significantly improve left-ventricular systolic pressure and +dp/dt max, reduce the E/E′ ratio, left ventricular end diastolic pressure, −dp/dt max and Tau in diabetic rats. Conclusions: Sitagliptin might have a myocardial protective effect by inhibiting apoptosis, inflammation, lipid accumulation and myocardial fibrosis in diabetic rats, for a potential role in improving left-ventricular function in diabetes.

Keywords

• Diabetes mellitus
• Sitagliptin
• Myocardial remodeling
• Cardiac function