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.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Internal Medicine, State University of Campinas, UNICAMP, Campinas, SP, Brazil.
C T
CT
De Souza
A L
AL
Gasparetti
M
M
Pereira-da-Silva
E P
EP
Araújo
J B
JB
Carvalheira
M J A
MJ
Saad
A C
AC
Boschero
E M
EM
Carneiro
L A
LA
Velloso
D000064:Acclimatization / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D003080:Cold Temperature; D017931:DNA Primers; D004734:Energy Metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D007473:Ion Channels; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D020738:Leptin / Q000097:blood; D026901:Membrane Transport Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000071246:Uncoupling Protein 2
D001786:Blood Glucose; D017931:DNA Primers; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1