Peroxisome proliferator-activated receptor gamma coactivator-1-dependent uncoupling protein-2 expression in pancreatic islets of rats: a novel pathway for neural control of insulin secretion.
Diabetologia
; 46(11): 1522-31, 2003 Nov.
Article
em En
| MEDLINE
| ID: mdl-14576981
AIMS/HYPOTHESIS: Sympathetic inputs inhibit insulin secretion through alpha2-adrenergic receptors coupled with Gi protein. High adrenergic tonus generated by exposure of homeothermic animals to cold reduces insulin secretion. In this study we evaluate the participation of UCP-2 in cold-induced regulation of insulin secretion. METHODS: Static insulin secretion studies, western blotting and immunohistochemistry were used in this investigation. RESULTS: Exposure of rats to cold during 8 days promoted 60% ( n=15, p<0.05) reduction of basal serum insulin levels concentration accompanied by reduction of the area under insulin curve during i.p. GTT (50%, n=15, p<0.05). Isolated islets from cold-exposed rats secreted 57% ( n=6, p<0.05) less insulin following a glucose challenge. Previous sympathectomy, partially prevented the effect of cold exposure upon insulin secretion. Islets isolated from cold-exposed rats expressed 51% ( n=6, p<0.5) more UCP-2 than islets from control rats, while the inhibition of UCP-2 expression by antisense oligonucleotide treatment partially restored insulin secretion of islets obtained from cold-exposed rats. Cold exposure also induced an increase of 69% ( n=6, p<0.05) in PGC-1 protein content in pancreatic islets. Inhibition of islet PGC-1 expression by antisense oligonucleotide abrogated cold-induced UCP-2 expression and partially restored insulin secretion in islets exposed to cold. CONCLUSION/INTERPRETATION: Our data indicate that sympathetic tonus generated by exposure of rats to cold induces the expression of PGC-1, which participates in the control of UCP-2 expression in pancreatic islets. Increased UCP-2 expression under these conditions could reduce the beta-cell ATP/ADP ratio and negatively regulate insulin secretion.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Fatores de Transcrição
/
Ilhotas Pancreáticas
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Proteínas Mitocondriais
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Aclimatação
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Insulina
Limite:
Animals
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Alemanha