Apelin‑13 ameliorates metabolic and cardiovascular disorders in a rat model of type 2 diabetes with a high‑fat diet.

Abstract

Apelin has been reported to be associated with multiple physiological processes in the cardiovascular system. The aim of the present study was to investigate the effects of Apelin‑13 administration on cardiac function, hyperglycemia, insulin resistance (IR), dyslipidemia, endothelial function, inflammation and glucose metabolism in type 2 diabetic Goto‑Kakizaki (GK) rats, and compare the protective effects of Apelin‑13 with metformin or atorvastatin. In the present study, type 2 diabetes was induced in male Goto‑Kakizaki (GK) rats fed with high‑fat diet (HFD). Simultaneously, the rats were treated with metformin (350mg/kg/d, by gavage), atorvastatin (50mg/kg/d, by gavage) or Apelin‑13 (200µg/kg/d, intraperitoneal injection) once daily for 4 consecutive weeks. Hemodynamic parameters were examined by RM6240BD multi‑channel physiological signal monitoring. Fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment for insulin resistance (HOMA‑IR), total cholesterol (TC), triglyceride (TG), high density lipoprotein‑cholesterol (HDL‑C), low density lipoprotein‑cholesterol (LDL‑C), endothelin‑1 (ET‑1), nitric oxide (NO), constitutive nitric oxide synthase (cNOS) activity, tumor necrosis factor‑α (TNF‑α), leptin and Apelin‑12 levels were measured. Western blotting was performed to determine the levels of Apelin‑12, glucose transporter 4 (GLUT4) and phosphorylated (p)‑5'adenosine monophosphate‑activated protein kinase (AMPK) α2. It was demonstrated that Apelin‑13 decreased heart rate, left ventricular end‑diastolic pressure, FPG, FINS, HOMA‑IR, TC, TG, LDL‑C, ET‑1, TNF‑α and leptin, whereas it increased the rise and fall of maximum rate of left ventricular pressure, HDL‑C, NO, cNOS activity and Apelin‑12 compared with the GK‑HFD group. In addition, GLUT4 and p‑AMPKα2 levels in myocardial tissues were elevated by administration of Apelin‑13. This protective effect of Apelin‑13 was comparable to that of metformin or atorvastatin. Overall, the present study demonstrated that administration ofApelin‑13 may be a promising therapeutic agent for the treatment of type 2 diabetes and metabolic syndrome.