ORCID
- Affourtit, Charles: 0000-0003-1776-9943
Abstract
Glucose-stimulated insulin secretion (GSIS) by pancreatic β 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 β 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.
DOI
10.1016/j.freeradbiomed.2010.12.020
Publication Date
2011-03-01
Publication Title
Free Radic Biol Med
Volume
50
Issue
5
Organisational Unit
School of Biomedical Sciences
Keywords
Animals, Antioxidants, Cell Line, Tumor, Diabetes Mellitus, Type 2, Energy Metabolism, Gene Knockdown Techniques, Glucose, Insulin, Insulin Secretion, Insulin-Secreting Cells, Ion Channels, Metalloporphyrins, Mice, Mitochondria, Mitochondrial Proteins, Rats, Reactive Oxygen Species, Uncoupling Protein 2
First Page
609
Last Page
616
Recommended Citation
Affourtit, C., Jastroch, M., & Brand, M. (2011) 'Uncoupling protein-2 attenuates glucose-stimulated insulin secretion in INS-1E insulinoma cells by lowering mitochondrial reactive oxygen species.', Free Radic Biol Med, 50(5), pp. 609-616. Available at: https://doi.org/10.1016/j.freeradbiomed.2010.12.020
