Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/195595
Type: Artigo de periódico
Title: Selective Impairment Of Insulin Signalling In The Hypothalamus Of Obese Zucker Rats.
Author: Carvalheira, J B C
Ribeiro, E B
Araújo, E P
Guimarães, R B
Telles, M M
Torsoni, M
Gontijo, J A R
Velloso, L A
Saad, M J A
Abstract: By acting in the brain, insulin suppresses food intake. However, little is known with regard to insulin signalling in the hypothalamus in insulin-resistant states. Western blotting, immunohistochemistry and polymerase chain reaction assays were combined to compare in vivo hypothalamic insulin signalling through the PI3-kinase and MAP kinase pathways between lean and obese Zucker rats. Intracerebroventricular insulin infusion reduced food intake in lean rats to a greater extent than that observed in obese rats, and pre-treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The relative abundance of IRS-2 was considerably higher than that of IRS-1 in hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of Akt in hypothalamus were decreased in obese rats compared to lean rats. These effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin stimulated the phosphorylation of MAP kinase equally in lean and obese rats. This study provides direct measurements of insulin signalling in hypothalamus, and documents selective resistance to insulin signalling in hypothalamus of Zucker rats. These findings provide support for the hypothesis that insulin could have anti-obesity actions mediated by the PI3-kinase pathway, and that impaired insulin signalling in hypothalamus could play a role in the development of obesity in this animal model of insulin-resistance.
Subject: Animals
Blood Glucose
Body Weight
Hypothalamus
Injections, Intraventricular
Insulin
Insulin Receptor Substrate Proteins
Intracellular Signaling Peptides And Proteins
Male
Obesity
Phosphoproteins
Phosphorylation
Phosphoserine
Rats
Rats, Zucker
Reference Values
Signal Transduction
Rights: fechado
Identifier DOI: 10.1007/s00125-003-1246-x
Address: http://www.ncbi.nlm.nih.gov/pubmed/14600817
Date Issue: 2003
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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