Effects of chronic ghrelin administration on metabolic profile, S100A4 levels, and cardiohepatic histopathology in type 2 diabetic rats

INTRODUCTION: Each year, nearly 18 million deaths occur due to cardiovascular diseases, and diabetes mellitus (DM) as well as hypertension are recognized as major underlying risk factors.
METHODS: The present study was designed to evaluate the impact of ghrelin on the blood lipid profile, LDH, serum and hepatic S100A4 levels, and liver and cardiac histology in a high fat diet-HFD/ streptozotocin-induced animal model of type 2 DM (T2DM).
RESULTS: HbA1c, LDL, cholesterol and triglyceride levels were significantly increased in the untreated T2DM group compared to controls, whereas HDL and LDH levels were decreased. In the T2DM+Metformin group, LDL, cholesterol, triglyceride and HbA1c levels were reduced, while HDL and LDH levels were increased compared to the T2DM group. In the T2DM+Ghrelin group, LDL levels were significantly increased whereas HDL, cholesterol, triglyceride and HbA1c levels were decreased relative to untreated diabetic animals. Serum and hepatic S100A4 levels were significantly increased in T2DM group, however ghrelin treatment significantly reduced hepatic S100A4 levels. Histological evaluation of cardiac tissue in untreated diabetic rats revealed structural irregularities, cardiomyocyte degeneration, reduced cell size, myocardial damage, and lymphatic infiltration. These diabetes-induced myocardial alterations were markedly improved by ghrelin or metformin treatment. In liver tissue, extensive hepatocyte damage, necrosis, and cellular degeneration were observed in the T2DM group, whereas both treatments reduced lymphocytic infiltration and hepatocellular damage.
DISCUSSION AND CONCLUSION: In conclusion, the results indicate that ghrelin may represent a potential therapeutic candidate for attenuating T2DM-related structural cardiac and hepatic damage; however, additional investigations are required to confirm these effects.

Keywords: Diabetes, ghrelin, lipid profile, metformin, neuropeptide, S100A4.