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
2010-12-11
Publication Title
Free Radic Biol Med
Volume
50
Issue
5
First Page
609
Last Page
616
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
Recommended Citation
Affourtit, C., Jastroch, M., & Brand, M. (2010) '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
