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 (350 mg/kg/d, by gavage), atorvastatin (50 mg/kg/d, by gavage) or Apelin-13 (200 µg/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.

Relationships of apelin concentration and APLN T-1860C polymorphism with obesity in Thai children

“…Additionally, TC and TG are predictors of the balance of lipid metabolism, while a previous study also noted that individuals with high TC/HDL-C or LDL-C/HDL-C ratios had greater cardiovascular risk [28] because these ratios reflected the balance between transport of cholesterol to peripheral tissues and reverse transport to the liver. Furthermore, a recent study in a rat model showed that apelin improved dyslipidaemia by decreasing TC, TG and LDL-C, and increasing HDL-C concentration [29]. Overall, our findings in Thai children suggest that apelin might provide an inverse association with cardiometabolic risks.…”

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions

“…However, some authors have reported proinflammatory action of APLN [104]: in a clinical study performed by Heinonen et al patients with metabolic syndrome showed high level of APLN and TNF-α [105] while other studies revealed that APLN mitigates hepatic macrophage infiltration and TNF-α expression and reduces myocardial inflammation induced by diabetes condition or sepsis shock [106][107][108][109].…”

Potential Therapeutic Role for Apelin and Related Peptides in Diabetes: An Update

“…apelin-13 (200 µg/kg bw for 4 weeks) on cardiac function and metabolic status have also been observed in obese diabetic Goto-Kakizaki (GK) rats (T2DM model). 79 Such benefits may be linked to apelin-induced sphingosine kinase 1 mediated inhibition of transforming growth factor beta (TGF-β). 80 Thus, TGF-β is a proinflammatory cytokine that is upregulated in diabetes 81 and induces cardiac fibrosis alongside extra cellular matrix protein deposition, 82 representing key risk factors in cardiac hypertrophy.…”