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Uncoupling protein-2 attenuates glucose-stimulated insulin secretion in INS-1E insulinoma cells by lowering mitochondrial reactive oxygen species.

Authors: Affourtit, C  Jastroch, M  Brand, MD 
Citation: Affourtit C, etal., Free Radic Biol Med. 2011 Mar 1;50(5):609-16. doi: 10.1016/j.freeradbiomed.2010.12.020. Epub 2010 Dec 21.
Pubmed: (View Article at PubMed) PMID:21172424
DOI: Full-text: DOI:10.1016/j.freeradbiomed.2010.12.020

Glucose-stimulated insulin secretion (GSIS) by pancreatic beta cells is regulated by mitochondrial uncoupling protein-2 (UCP2), but opposing phenotypes, GSIS improvement and impairment, have been reported for different Ucp2-ablated mouse models. By measuring mitochondrial bioenergetics in attached INS-1E insulinoma cells with and without UCP2, we show that UCP2 contributes to proton leak and attenuates glucose-induced rises in both respiratory activity and the coupling efficiency of oxidative phosphorylation. Strikingly, the GSIS improvement seen upon UCP2 knockdown in INS-1E cells is annulled completely by the cell-permeative antioxidant MnTMPyP. Consistent with this observation, UCP2 lowers mitochondrial reactive oxygen species at high glucose levels. We conclude that UCP2 plays both regulatory and protective roles in beta cells by acutely lowering GSIS and chronically preventing oxidative stress. Our findings thus provide a mechanistic explanation for the apparently discrepant findings in the field.

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CRRD Object Information
CRRD ID: 7204422
Created: 2012-12-18
Species: All species
Last Modified: 2012-12-18
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.