Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2009 Aug 28;284(35):23602-12. doi: 10.1074/jbc.M109.024323. Epub 2009 Jun 22.

Transient oxidative stress damages mitochondrial machinery inducing persistent beta-cell dysfunction.

Author information

1
Department of Cell Physiology, Faculty of Medicine, University of Geneva, rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland.

Abstract

Transient exposure of beta-cells to oxidative stress interrupts the transduction of signals normally coupling glucose metabolism to insulin secretion. We investigated putative persistence of effects induced by one transient oxidative stress (200 microm H(2)O(2), 10 min) on insulin secreting cells following recovery periods of days and weeks. Three days after oxidative stress INS-1E cells and rat islets exhibited persistent dysfunction. In particular, the secretory response to 15 mm glucose was reduced by 40% in INS-1E cells stressed 3 days before compared with naïve cells. Compared with non-stressed INS-1E cells, we observed reduced oxygen consumption (-43%) and impaired glucose-induced ATP generation (-46%). These parameters correlated with increased mitochondrial reactive oxygen species formation (+60%) accompanied with down-regulation of subunits of the respiratory chain and decreased expression of genes responsible for mitochondrial biogenesis (TFAM, -24%; PGC-1alpha, -67%). Three weeks after single oxidative stress, both mitochondrial respiration and secretory responses were recovered. Moreover, such recovered INS-1E cells exhibited partial resistance to a second transient oxidative stress and up-regulation of UCP2 (+78%) compared with naïve cells. In conclusion, one acute oxidative stress induces beta-cell dysfunction lasting over days, explained by persistent damages in mitochondrial components.

PMID:
19546218
PMCID:
PMC2749135
DOI:
10.1074/jbc.M109.024323
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center