Effect of resveratrol on sirtuins expression and cardiac complications in diabetes

Abstract

Sirtuins are the protein deacetylases, which are linked to metabolic diseases and aging. There are seven sirtuins present in cell, whose regulation in diabetic heart is yet to be explored. Resveratrol is a well-known activator of SIRT-1, but its effect on other sirtuins is not yet clear. In the present study, we focused to find out the expression and regulation of all sirtuins in diabetic heart with the effect of resveratrol administration on them. We have induced T1DM rat model using steptozotocin and T2DM rat model by feeding high fructose diet for a period of eight weeks and analyzed the myocardial changes. Resveratrol was administrated to both the models simultaneously. Increased oxidative stress and cardiac phenotype alterations shows the induction of cardiac abnormalities in both models. We have observed decreased SIRT-1 and increased SIRT-3 activity in the T2DM rat heart. Moreover, in case of T1DM, gene and protein expression of all sirtuins was down, except SIRT-2 whose protein levels were increased. Administration of resveratrol prevented the alteration in SIRT-1 in T2DM and SIRT-1, 2, 3 and SIRT-5 in T1DM rat heart. Altered level of protein acetylation was observed corresponding to the changes in sirtuins. In conclusion, sirtuins are perturbed in both types of diabetic heart and can be considered as druggable target for therapeutic intervention.

Keywords: Acetylation; Diabetic cardiomyopathy; Resveratrol; Sirtuins; T1DM; T2DM.