Vol. 12, Issue 5 (2023)

Author(s):
Gnanapragasam Arunachalam

Abstract:
Intracellular accumulation of excess reactive oxygen species (ROS) have been implicated to play an important role in the pathogenesis of type 2 diabetes (T2D)-associated cardiovascular disease (CVD) including the deleterious effects in the cardiovascular system such as cardiomyocyte apoptosis and necrosis. Thus, in the current study, we explored the cellular mechanisms whereby cardiomyocytes (H9C2) exposed to either with normal glucose (NG, 5.5 mM) or high glucose (HG, 25 mM) and the expressions of cell survival/apoptotic markers were accessed by immuno blotting. These results revealed that HG exposure caused a significant decrease in anti-apoptotic Sirtuin 1 (SIRT1), Bcl-2 expressions with a concomitant increase in the Ac-p53 expression (pro-apoptotic). Interestingly, treatment with the anti-diabetic drug, metformin prevented the deleterious effects (apoptosis) by up-regulating the SIRT1 expression and its downstream signalling in HG-exposed cardiomyocytes. These results indicate that in a diabetic milieu, persistent HG exposure enhances the activation of p53, but down regulates the expression of SIRT1 and Bcl-2 proteins. Furthermore, metformin attenuated the detrimental effects of HG-exposure suggesting that in addition to its anti-hyperglycaemic action, metformin has therapeutic effects in cardiovascular function, which is more beneficial in T2D associated co-morbid conditions.