In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 33 ( 2008-08-19), p. 12057-12062
Abstract:
In pancreatic β-cells, uncoupling protein 2 (UCP2) influences mitochondrial oxidative phosphorylation and insulin secretion. Here, we show that α-cells express significantly higher levels of UCP2 than do β-cells. Greater mitochondrial UCP2-related uncoupling was observed in α-cells compared with β-cells and was accompanied by a lower oxidative phosphorylation efficiency (ATP/O). Conversely, reducing UCP2 activity in α-cells was associated with higher mitochondrial membrane potential generated by glucose oxidation and with increased ATP synthesis, indicating more efficient metabolic coupling. In vitro , the suppression of UCP2 activity led to reduced glucagon secretion in response to low glucose; however, in vivo , fasting glucagon levels were normal in UCP2 −/− mice. In addition to its effects on secretion, UCP2 played a cytoprotective role in islets, with UCP2 −/− α-cells being more sensitive to specific death stimuli. In summary, we demonstrate a direct role for UCP2 in maintaining α-cell function at the level of glucose metabolism, glucagon secretion, and cytoprotection.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0710434105
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2008
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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