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Type: Artigo de periódico
Title: Molecular and functional resistance to insulin in hypothalamus of rats exposed to cold
Author: Torsoni, MA
Carvalheira, JB
Pereira-Da-Silva, M
de Carvalho, MA
Saad, MJA
Velloso, LA
Abstract: Insulin and leptin act in the hypothalamus, providing robust anorexigenic signals. The exposure of homeothermic animals to a cold environment leads to increased feeding, accompanied by sustained low levels of insulin and leptin. In the present study, the initial and intermediate steps of the insulin-signaling cascade were evaluated in the hypothalamus of cold-exposed Wistar rats. By immunohistochemistry, most insulin receptor (IR) and insulin receptor substrate-2 (IRS-2) immunoreactivity localized to the arcuate nucleus. Basal levels of tyrosine phosphorylation of IR and IRS-2 were increased in cold-exposed rats compared with rats maintained at room temperature. However, after an acute, peripheral infusion of exogenous insulin, significantly lower increases of IR and IRS-2 tyrosine phosphorylation were detected in the hypothalamus of cold-exposed rats. Insulin-induced association of p85/phosphatidylinositol 3-kinase with IRS-2, Ser(473) phosphorylation of Akt, and tyrosine phosphorylation of ERK was significantly reduced in the hypothalamus of cold-exposed rats. To test the hypothesis of functional impairment of insulin signaling in the hypothalamus, intracerebroventricularly cannulated rats were acutely treated with insulin, and food ingestion was measured over a period of 12 h. Cold-exposed animals presented a significantly lower insulin-induced reduction in food consumption compared with animals maintained at room temperature. Hence, the present studies reveal that animals exposed to cold are resistant, both at the molecular and the functional level, to the actions of insulin in the hypothalamus.
Subject: insulin receptor
insulin substrate receptor-2
food ingestion
Country: EUA
Editor: Amer Physiological Soc
Citation: American Journal Of Physiology-endocrinology And Metabolism. Amer Physiological Soc, v. 285, n. 1, n. E216, n. E223, 2003.
Rights: embargo
Identifier DOI: 10.1152/ajpendo.00031.2003
Date Issue: 2003
Appears in Collections:Unicamp - Artigos e Outros Documentos

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