Document Detail

Mitochondrial uncoupling protein 2 in pancreatic β-cells.
MedLine Citation:
PMID:  21029310     Owner:  NLM     Status:  In-Process    
Pancreatic β-cells have remarkable bioenergetics in which increased glucose supply upregulates the cytosolic ATP/ADP ratio and increases insulin secretion. This arrangement allows glucose-stimulated insulin secretion (GSIS) to be regulated by the coupling efficiency of oxidative phosphorylation. Uncoupling protein 2 (UCP2) modulates coupling efficiency and may regulate GSIS. Initial measurements of GSIS and glucose tolerance in Ucp2(-/-) mice supported this model, but recent studies show confounding effects of genetic background. Importantly, however, the enhancement of GSIS is robustly recapitulated with acute UCP2 knockdown in INS-1E insulinoma cells. UCP2 protein level in these cells is dynamically regulated, over at least a fourfold concentration range, by rapid proteolysis (half-life less than 1 h) opposing regulated gene transcription and mRNA translation. Degradation is catalysed by the cytosolic proteasome in an unprecedented pathway that is currently known to act only on UCP2 and UCP3. Evidence for proteasomal turnover of UCP2 includes sensitivity of degradation to classic proteasome inhibitors in cells, and reconstitution of degradation in vitro in mitochondria incubated with ubiquitin and the cytosolic 26S proteasome. These dynamic changes in UCP2 content may provide a fine level of control over GSIS in β-cells.
M D Brand; N Parker; C Affourtit; S A Mookerjee; V Azzu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  12 Suppl 2     ISSN:  1463-1326     ISO Abbreviation:  Diabetes Obes Metab     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  134-40     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Buck Institute for Age Research, Novato, CA 94945, USA.
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Grant Support
P01AG025901/AG/NIA NIH HHS; P30 AG025708/AG/NIA NIH HHS; PL1AG032118/AG/NIA NIH HHS; R01 AG033542/AG/NIA NIH HHS; //Medical Research Council

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