Is the Effect of Caloric Restriction on Type 2 Diabetes Mellitus in Rats Mediated Via Sirtuin-1?

Background: Type 2 diabetes mellitus is a long-lasting disease that can be improved but not cured. Insulin resistance is the initial disorder occurring in type 2 diabetes mellitus even before the development of hyperglycemia. Both insulin resistance and P-cell dysfunction are linked with obesity especially the visceral adiposity. It was reported that over nutrition and aging, which are the chief precipitating factors for diabetes, are positively correlated with reduced sirtuin-1 (SIRT1) activity resulting in hyperglycemia and hyperlipidemia. Therefore, reestablishing the normal level and activity of SIRT-1in type 2 diabetes mellitus (T2DM) may be a promising method of treating diabetes. SIRT1 is induced in several tissues during CR and energy deprivation is the major activator of SIRT1 over expression which will respond via stimulating lipolysis through increasing the expression of triglyceride lipase. SIRT1 also inhibits lipogenesis. Aim of the Work: Is to assess the impact of caloric restric-tion on SIRT1 in the liver and pancreas of type 2 diabetic rats. Material and Methods: 32 male albino rats were included in the study and divided into group I: Control group, group II: Diabetic group, group III: Pre-diabetes CR group and group IV: Post-diabetes CR group. After finishing the experimental study we measured the serum glucose level, serum insulin level, HOMA-IR, SIRT 1 level and activity in liver and pancreas of adult male rats. Results: Our results revealed that both pre-diabetes CR and post-diabetes CR groups were associated with significant improvement of SIRT1 level and activity in liver and pancreas of T2DM rats in addition to their beneficial effect on improving the insulin sensitivity and thus reducing insulin resistance and concomitant hyperglycemia. Conclusion: The decrease in SIRT1 associated with diabetes was actually attenuated by the 30% caloric restriction leading to significant improvement in T2DM.