Proton leak exerts stronger control over ATP/ADP in mitochondria from clonal pancreatic β-cells (INS-1E) than in those from rat skeletal muscle, due to the higher proton conductance of INS-1E mitochondria [Affourtit and Brand (2006) Biochem. J. 393, 151–159]. In the present study, we demonstrate that high proton leak manifests itself at the cellular level too: the leak rate (measured as myxothiazol-sensitive, oligomycin-resistant respiration) was nearly four times higher in INS-1E cells than in myoblasts. This relatively high leak activity was decreased more than 30% upon knock-down of UCP2 (uncoupling protein-2) by RNAi (RNA interference). The high contribution of UCP2 to leak suggests that proton conductance through UCP2 accounts for approx. 20% of INS-1E respiration. UCP2 knock-down enhanced GSIS (glucose-stimulated insulin secretion), consistent with a role for UCP2 in β-cell physiology. We propose that the high mitochondrial proton leak in β-cells is a mechanism which amplifies the effect of physiological UCP2 regulators on cytoplasmic ATP/ADP and hence on insulin secretion.
Skip Nav Destination
Article navigation
January 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 11 2007
Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion
Charles Affourtit;
Charles Affourtit
1
1MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 0XY, U.K.
1To whom correspondence should be addressed (email ca@mrc-dunn.cam.ac.uk).
Search for other works by this author on:
Martin D. Brand
Martin D. Brand
1MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 0XY, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 18 2007
Revision Received:
September 03 2007
Accepted:
September 10 2007
Accepted Manuscript online:
September 10 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 409 (1): 199–204.
Article history
Received:
July 18 2007
Revision Received:
September 03 2007
Accepted:
September 10 2007
Accepted Manuscript online:
September 10 2007
Citation
Charles Affourtit, Martin D. Brand; Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion. Biochem J 1 January 2008; 409 (1): 199–204. doi: https://doi.org/10.1042/BJ20070954
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.