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 language | English (US) |
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Pages (from-to) | 216-222 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 300 |
Issue number | 1 |
DOIs | |
State | Published - 2003 |
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