SirT3 regulates diabetogenic effects caused by arsenic: An implication for mitochondrial complex II modification

Toxicol Lett. 2019 Feb;301:24-33. doi: 10.1016/j.toxlet.2018.10.025. Epub 2018 Oct 29.


Background: A large body of evidence indicates that accumulation of oxidative stress originated from impaired mitochondrial respiratory chain is the main cause for the development of numerous diseases including diabetes and cancer. Arsenic exposure is a potential risk factor for type 2 diabetes development which, by disrupting mitochondrial respiration and SirT3 enzyme activity, enhances reactive oxygen species (ROS) level and evokes oxidative stress. In this study the impact of arsenic exposure on the mitochondrial function and SirT3 from rat's liver were examined in the presence or absence of metformin and berberine.

Methods: Serum glucose and insulin levels were assessed in rats exposed to the diabetogenic concentration of arsenic. Isolated hepatocytes and mitochondria were then further evaluated to determine any deleterious consequences.

Results: Diabetogenesis triggered by arsenic contributed to the mitochondrial ROS overproduction, impaired complex II activity, glucose homeostasis, glucose tolerance and insulin sensitivity. An increased SirT3 level indicated the compensatory mechanism to deal with this condition. Protective effect of metformin and berberine against these toxic insults were found to be associated with the mitochondrial SirT3 pathway. This pathway through the regulation of mitochondria-associated ROS production and glucose homeostasis in the liver may play a crucial role against the diabetogenic effect of arsenic.

Keywords: Arsenic; Complex II; Diabetes; Mitochondria; Oxidative stress; SirT3.

MeSH terms

  • Animals
  • Arsenic / adverse effects*
  • Berberine / pharmacology
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / metabolism
  • Electron Transport Complex II / metabolism*
  • Gene Expression Regulation*
  • Glutathione / metabolism
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Insulin Resistance
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Metformin / pharmacology
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sirtuins / metabolism*


  • Blood Glucose
  • Reactive Oxygen Species
  • SIRT3 protein, rat
  • Berberine
  • Malondialdehyde
  • Metformin
  • Electron Transport Complex II
  • Sirtuins
  • Glutathione
  • Arsenic