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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-12-7
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pubmed:abstractText |
Proton leak exerts stronger control over ATP/ADP in mitochondria from clonal pancreatic beta-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 beta-cell physiology. We propose that the high mitochondrial proton leak in beta-cells is a mechanism which amplifies the effect of physiological UCP2 regulators on cytoplasmic ATP/ADP and hence on insulin secretion.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
409
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
199-204
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17824844-Animals,
pubmed-meshheading:17824844-Cytoplasm,
pubmed-meshheading:17824844-Glucose,
pubmed-meshheading:17824844-Insulin,
pubmed-meshheading:17824844-Insulin-Secreting Cells,
pubmed-meshheading:17824844-Ion Channels,
pubmed-meshheading:17824844-Membrane Potentials,
pubmed-meshheading:17824844-Methacrylates,
pubmed-meshheading:17824844-Mitochondria,
pubmed-meshheading:17824844-Mitochondrial Proteins,
pubmed-meshheading:17824844-Oligomycins,
pubmed-meshheading:17824844-Oxygen,
pubmed-meshheading:17824844-Oxygen Consumption,
pubmed-meshheading:17824844-Phosphorylation,
pubmed-meshheading:17824844-RNA Interference,
pubmed-meshheading:17824844-Rats,
pubmed-meshheading:17824844-Thiazoles
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pubmed:year |
2008
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pubmed:articleTitle |
Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion.
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pubmed:affiliation |
MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 0XY, UK. ca@mrc-dunn.cam.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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