Effect of metformin on Sirtuin-1 disorders associated with diabetes in male rats

Abstract

Background: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, hyperinsulinaemia and hyperglycaemia. Increased glucose production through abnormally elevated hepatic gluconeogenesis is central to the manifestation of hyperglycaemia in T2DM. Metformin corrects hyperglycaemia mainly through inhibition of gluconeogenesis. Sirtuin 1 (SIRT1) has been identified as regulator of gluconeogenic gene expression. The present study aimed to evaluate the effect of metformin on SIRT1 level and activity in liver and pancreas of diabetic rats. Further, the possible role of SIRT1 on metabolic disorders associated with diabetes mellitus, including serum levels of glucose, insulin, triglyceride (TG) and high density lipoprotiens (HDL), will be explored.

Methods: Thirty-two male albino rats were divided into control group (GpI), diabetic (DM) group (GpII), (metformin + DM) group (GpIII) administered 120 mg/kg metformin daily for 1 month before induction of diabetes, (DM + metformin) group (GpIV) administered 250 mg/kg metformin daily for 1 month after induction of diabetes. At the end of the study, BMI%, serum levels of glucose, insulin, TG and HDL, HOMA, SIRT1 level and activity in liver and pancreas and pancreatic DNA ladder were assessed.

Results: Our results showed significant decrease in serum glucose, insulin and TG levels and HOMA; significant increase in HDL level and SIRT1 level and activity in liver and pancreas beside the marked disappearance of pancreatic apoptosis in GpIII & IV relative to GpII. Regarding BMI%, it showed no significant changes in GpIV relative to GpII. No significant change was recorded between GpIII and GpIV regarding all studied parameters except on serum TG.

Conclusion: Lowered SIRT1 in diabetes was improved by the administration of Metformin. Consequently, the pathophysiological disorders associated with T2DM were improved.

Keywords: DM, Metformin, SIRT1, Pancreatic apoptosis