Taurine improves low-level inorganic arsenic-induced insulin resistance by activating PPARγ-mTORC2 signalling and inhibiting hepatic autophagy

J Cell Physiol. 2019 Apr;234(4):5143-5152. doi: 10.1002/jcp.27318. Epub 2018 Oct 26.


Inorganic arsenic (iAs) is reportedly associated with the increased incidence of type 2 diabetes in the population. Here, we found that iAs exposure significantly decreased the expression of glycolytic genes and glycogen content and increased gluconeogenesis gene levels in C57/BL6J mice. The expression of peroxisome proliferator-activated receptor γ (PPARγ), and mechanistic target of rapamycin complex 2 (mTORC2) were decreased in the livers of iAs-treated mice. Furthermore, in iAs-treated HepG2 cells, we found that PPARγ agonist rosiglitazone (RGS) increased the expression of mTORC2, inhibited autophagy, and improved glucose metabolism. mTORC2 agonist palmitic acid inhibited autophagy and improved glucose metabolism as well as the autophagosome formation inhibitor 3-methyladenine. Taurine, a natural compound, reversed impaired glucose metabolism and decreased expression of PPARγ and mTORC2 induced by iAs in mice liver and HepG2 cells. These data indicated that taurine administration could ameliorate iAs-induced insulin resistance through activating PPARγ-mTORC2 signalling and subsequently inhibiting hepatic autophagy.

Keywords: PPARγ; inorganic arsenic; insulin resistance; mTORC2; taurine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenic Trioxide / toxicity*
  • Autophagy / drug effects*
  • Autophagy-Related Proteins / metabolism
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Gluconeogenesis / drug effects
  • Glycolysis / drug effects
  • Hep G2 Cells
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Insulin Resistance*
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Mechanistic Target of Rapamycin Complex 2 / metabolism*
  • Mice, Inbred C57BL
  • PPAR gamma / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Taurine / pharmacology*


  • Autophagy-Related Proteins
  • Blood Glucose
  • PPAR gamma
  • PPARG protein, human
  • Pparg protein, mouse
  • Taurine
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt
  • Arsenic Trioxide