Effect of a Metformin Derivative Containing Nitrile Group on Some Biochemical Variables in Rabbits Induced by Alloxane

Abstract

Background: Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Dipeptidyl peptidase-4 (DPP-4) degrades some enterocrinins, which are responsible for glucose metabolism, protection in cardiometabolic disease and immune regulation. The aim of this study is to prepare the nitrile derivative of metformin to act as an inhibitor of the DPP-4 enzyme, which is responsible for regulating blood sugar in relation to the secretion of insulin from beta cells in the pancreas. Methods: The preparation of the nitrile derivative obtained by the reaction of metformin and 3-bromopropanenitrile in methanol, characterized by 1HNMR and 13CNMR. Alloxan was injected to rabbits to induced diabetes. New synthesized drugs were given to rabbits for two weeks. Results: The results of biochemical study show significant decreases in the level of glucose, glucagon, the activity of DPP-4, significant increase in the level of insulin, and no significant difference in C-peptide level in treatment group compared with the diabetic group.

Conclusion: Decrease in the level of glucose, DPP-4 and glucagon were observed in the treatment group compared with the diabetes control group with its return to the normal level due to the effectiveness of the proposed drug in improving the sensitivity of cells to insulin and the transit of glucose molecules from the blood into the cells.