Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells

Biochem Biophys Res Commun. 2003 Jan 3;300(1):216-22. doi: 10.1016/s0006-291x(02)02832-2.


Pancreatic beta-cells exposed to hyperglycemia produce reactive oxygen species (ROS). Because beta-cells are sensitive to oxidative stress, excessive ROS may cause dysfunction of beta-cells. Here we demonstrate that mitochondrial ROS suppress glucose-induced insulin secretion (GIIS) from beta-cells. Intracellular ROS increased 15min after exposure to high glucose and this effect was blunted by inhibitors of the mitochondrial function. GIIS was also suppressed by H(2)O(2), a chemical substitute for ROS. Interestingly, the first-phase of GIIS could be suppressed by 50 microM H(2)O(2). H(2)O(2) or high glucose suppressed the activity of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme, and inhibitors of the mitochondrial function abolished the latter effects. Our data suggested that high glucose induced mitochondrial ROS, which suppressed first-phase of GIIS, at least in part, through the suppression of GAPDH activity. We propose that mitochondrial overwork is a potential mechanism causing impaired first-phase of GIIS in the early stages of diabetes mellitus.

MeSH terms

  • Animals
  • Cell Line
  • Electron Transport / drug effects
  • Glucose / pharmacology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Iodoacetates / pharmacology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Superoxides / metabolism


  • Insulin
  • Iodoacetates
  • Reactive Oxygen Species
  • Superoxides
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Glucose