Metformin ameliorates diabetes with metabolic syndrome induced changes in experimental rats

Abstract

Objective: The present study was designed to evaluate potential effects of Metformin on various components of metabolic syndrome. Also to elucidate the underlying mechanisms: DPP-IV, anti-inflammatory, antioxidant pathways. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. The HFD were fed to rats for 10 weeks to induce metabolic syndrome. At the end of 3 weeks, diabetes was induced by a single STZ injection (40 mg/kg body wt). Metformin (100 mg/kg) was administered to rat from 4^th to 10^th weeks daily and various parameters of Diabetes and metabolic syndrome were studied. Also to understand the mechanisms; DPP-IV pathway, anti-inflammatory, antioxidant parameters were studied. Biochemical indices of injury {pancreatic, liver and renal function} and histopathological assessment of injury was evaluated in experimental groups. Results: Metformin treatment ameliorated the deleterious effects associated with metabolic syndrome and diabetes. Metformin favorably modulated various parameters: anti-diabetic (reduced Blood glucose, HbA1c, HOMA-IR, increased serum insulin, HOMA-? and restoration of pancreatic function), Central obesity (reduced body weight, abdominal circumference (AC), thoracic circumference (TC), AC/TC ratio) and hypolipidemic (favorable lipid profile, artherogenic index). In addition significant restoration of cardiac injury as indicated by CPK-MB levels were observed. In addition, DPP-IV pathway (reduced serum DPP-IV), anti-inflammatory (reduced hs-CRP levels), antioxidant (reduced MDA) contributed to the beneficial effects of Metformin in diabetes with metabolic syndrome. The histopathological assessment confirmed the protective effects of Metformin on heart, thoracic aorta, pancreas, liver and kidney. Conclusion: Metformin treatment ameliorated the deleterious effects associated metabolic syndrome in the setting of diabetes mellitus. Beneficial effects of Metformin can be attributed to hypoglycemic, hypolipidemic, antioxidant, cardioprotective and anti-inflammatory effects.