الفهرس | Only 14 pages are availabe for public view |
Abstract Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of dipeptidyl peptidase-4 inhibitors alone or in combination with Pioglitazone, as treatment regimens for TID using Streptozotocin (STZ) induced TID model in rats. Daily oral administration of Sitagliptin (10 mg/kg), Vildagliptin (5 mg/kg) and Vildagliptin (5 mg/kg) in combination with Pioglitazone (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA1c. They increased serum insulin levels and decreased serum glucagon. They also showed an anti-oxidant activity by increasing GSH content and SOD activity with concomitant reduction of MDA and nitrite/nitrate contents. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared to diabetic one, which appeared in the normal cellular and architecture restoration of them in the islets of Langerhans. Conclusion: DPP-4 inhibitors alone or in combination with Pioglitazone have the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for type I diabetes. |