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

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2003 Oct 25

PMID 14576981

Citations 18

Authors

C T de Souza

A L Gasparetti

M Pereira-da-Silva

E P Araujo

J B Carvalheira

M J A Saad

A C Boschero

E M Carneiro

L A Velloso

Affiliations

Soon will be listed here.

Abstract

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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