Arsenic, mitochondrial Sirt3 and diabetogenesis

Accumulation of oxidative damage made by mitochondriotropic toxicants has been linked to the development of chronic diseases including diabetes and cancer. Arsenic is a diabetogenic metalloid which by interacting with mitochondrial normal function leads to reactive oxygen species (ROS) overproduction and oxidative stress. Sirtuins are a family of regulating enzymes and mitochondrially localized Sirt3 contributes mainly to the fine tuning of complex I activity and hence, ROS production as its activity’s byproduct. So we here discussed about the impact of arsenic exposure at the diabetogenic concentration on the mitochondrial function and SirT3. Serum glucose and insulin levels were assessed in rats following the arsenic exposure and isolated hepatocytes and mitochondria were then further assessed to determine any deleterious effects. Impairment in the complex II activity, glucose homeostasis, glucose tolerance and insulin sensitivity were observed. Increased SirT3 level probably is a compensatory mechanism to deal with the toxic insult. The SirT3 dependent regulation of mitochondria-associated ROS production and glucose homeostasis in the liver may play a crucial role against the diabetogenic effect of arsenic.