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

Koji Sakai, Kazuya Matsumoto, Takeshi Nishikawa, Mihoshi Suefuji, Kazuhiko Nakamaru, Yoshiaki Hirashima, Junji Kawashima, Tetsuya Shirotani, Kenshi Ichinose, Michael Brownlee, Eiichi Araki

Research output: Contribution to journalArticle

253 Scopus citations

Abstract

Pancreatic β-cells exposed to hyperglycemia produce reactive oxygen species (ROS). Because β-cells are sensitive to oxidative stress, excessive ROS may cause dysfunction of β-cells. Here we demonstrate that mitochondrial ROS suppress glucose-induced insulin secretion (GIIS) from β-cells. Intracellular ROS increased 15 min after exposure to high glucose and this effect was blunted by inhibitors of the mitochondrial function. GIIS was also suppressed by H2O2, a chemical substitute for ROS. Interestingly, the first-phase of GIIS could be suppressed by 50 μM H2O2. H2O2 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.

Original languageEnglish (US)
Pages (from-to)216-222
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume300
Issue number1
DOIs
StatePublished - Jan 14 2003

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Keywords

  • Diabetes mellitus
  • Electron transport system
  • Glyceraldehyde 3-phosphate dehydrogenase
  • Glycolysis
  • Hydrogen peroxide
  • Insulin secretion
  • Iodoacetates
  • Islets of Langerhans
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sakai, K., Matsumoto, K., Nishikawa, T., Suefuji, M., Nakamaru, K., Hirashima, Y., Kawashima, J., Shirotani, T., Ichinose, K., Brownlee, M., & Araki, E. (2003). Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic β-cells. Biochemical and Biophysical Research Communications, 300(1), 216-222. https://doi.org/10.1016/S0006-291X(02)02832-2