Etapas iniciais da ação insulinica em figado e musculo de ratos alimentados com dieta hiperlipidica

AUTOR(ES)
DATA DE PUBLICAÇÃO

1997

RESUMO

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of the cytosolic substrate, insulin receptor substrate-1 (IRS-I ), which in tum associates with and activates phosphatidylinositol 3-kinase (PI 3-kinase). Feeding diets high in fat content causes insulin resistance. However, the exact molecular mechanism is unknown. In the present study we have examined the levels and phosphorylation status of the insulin receptor, IRS-I, as well as the association between IRS-1/PI 3-kinase, in the tiver and musc1e of rats fed high-fat diet (59% saturated fat) by immunoblotting with specific antibodies. The levels and the insulin-stimulated autophosphorylation of the insulin receptor, as determined by immunoblotting with an antiphosphotyrosine antibody, are similar in the liver and musc1e in both the high fat-diet fed and chow-diet fed rats. In the liver, the IRS-I protein levels increased 51:1:17% (p<0,05) and in samples previously immunoprecipitated with anti-IRS-1 antibody and blotted with antiphosphotyrosine antibody, there was a increase in the insulin stimulated IRS-1 phosphorylation levels to 64:t22% (p<0,05) in the high fat-diet fed animaIs. In contrast, the insulin-stimulated phosphorylation of IRS-I in musc1e of high fat-diet fed rats was reduced to 50:1:12% (p<0,05), although there was no change in protein levels. The insulin-stimulated IRS-I association with PI 3-kinase decreased to 52:1:11% (p<0,05) in musc1e of the rats fed high fat-diet, but was no change in the liver. These data suggest that changes in the early steps of insulin signal transduction may have a role in the insulin resistance observed in high fat-fed animaIs

ASSUNTO(S)

insulina insulina - receptores

ACESSO AO ARTIGO

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