Mitigating effects of vildagliptin in experimental diabetes with metabolic syndrome

Abstract

Background: Vildagliptin has multiple beneficial effects reported in isolated studies like anti-diabetic, cardio protective, anti-inflammatory and antioxidant. However, there is no experimental evidence presently available with regard to the possible beneficial effects of vildagliptin on attenuating changes observed in metabolic syndrome co-existing with diabetes in experimental rats. Thus, the present study was designed to evaluate potential effects of vildagliptin on various components of metabolic syndrome. Also to elucidate the underlying mechanisms: DPP-IV, anti-inflammatory, antioxidant pathways were studied. 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 weight). Vildagliptin (10 mg/kg) was administered to rat from 5th to 10th 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. Immunohistochemistry of pancreas was done to assess beta cell mass. Results: The vildagliptin treatment ameliorated the deleterious effects associated with metabolic syndrome and diabetes. The beneficial effects demonstrated by vildagliptin on various parameters include: anti-diabetic (reduced blood glucose, HbA1c, HOMA-IR, increased serum insulin, HOMA-β and restoration of pancreatic function), central obesity (reduced body weight, abdominal circumference (AC), thoracic circumference (TC), AC/TC ratio) and hypolipidemic (favourable lipid profile, artherogenic index) activity. A significant restoration of cardiac injury as indicated by CPK-MB levels was observed. In addition, DPP-IV pathway (reduced serum DPP-IV), anti-inflammatory (reduced hs-CRP levels), and antioxidant (reduced MDA) contributed its beneficial effects in diabetes with metabolic syndrome model. The protective effects on heart, pancreas, liver and kidney were confirmed by histopathological report. The immunohistochemical report of pancreas showed preservation of beta cell mass in vildagliptin treated rats. Conclusions: Vildagliptin treatment ameliorates deleterious changes of diabetes with metabolic syndrome. Beneficial effects of vildagliptin can be attributed to hypoglycemic, hypolipidemic, antioxidant, cardioprotective and anti-inflammatory effects.