ADDITION OF SITAGLIPTIN TO REPAGLINIDE IMPROVES PANCREATIC ISLET PROLIFERATION AND INSULIN PRODUCTION IN EXPERIMENTALLY-INDUCED TYPE 2 DIABETES IN RATS

Document Type : Original Article

Author

Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt

Abstract

Type 2 diabetes mellitus is a complex heterogeneous group of metabolic conditions characterized by increased levels of blood glucose due to impairment in insulin action and/or insulin secretion. Exploring new drug therapies will benefit in preventing morbidity and mortality associated with diabetes as well as the growing health care costs. Sitagliptin is a highly selective DPP-4 inhibitor that has been shown to improve glycemic control and beta cell function. Repaglinide is a short acting insulin sectretagogue stimulating insulin release. The purpose of this study was to evaluate the effect of combining sitagliptin (5 mg/kg) and repaglinide (0.15 mg/kg & 0.3 mg/kg) on improving hyperglycemia and enhancing the pancreatic function in high fat diet/streptozotocin-induced type 2 diabetes mellitus rat model. The current results highlight a significant improvement in glycemic control and pancreatic insulin production upon addition of sitagliptin to repaglinide therapy. Repaglinide either alone or in combination was effective in preserving islet cell integrity. Further, immunohistochemical staining revealed significant higher insulin content in the combination groups compared to corresponding monotherapies. The combination therapy had a positive effect in lowering serum lipids. In conclusion, the present study reinforces the view of using gliptins in combination with repaglinide to enhance the glycemic control and lipid profile in patients with type 2 diabetes.

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