RESUMO
In the present study we have examined the levels and phosphorylation state of the insulin receptor and insulin receptor substrate 1 (IRS-1) as well as the association between IRS-1 and phosphatidylinositol 3-kinase (PI 3-kinase) in the liver and muscle of rats treated with glucagon. There was a decrease in the insulin-stimulated receptor and IRS-1 phosphorylation levels which was paralleled by a reduced association between IRS-1 and PI 3-kinase in vivo in the liver and muscle of glucagon-treated rats. These observations suggest that glucagon, probably acting through cAMP, may impair insulin signaling in the three early steps in insulin action after binding.
Assuntos
Glucagon/farmacologia , Insulina/farmacologia , Fígado/metabolismo , Músculo Esquelético/metabolismo , Fosfoproteínas/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Animais , Proteínas Substratos do Receptor de Insulina , Fígado/efeitos dos fármacos , Masculino , Músculo Esquelético/efeitos dos fármacos , Fosfatidilinositol 3-Quinases , Fosfoproteínas/efeitos dos fármacos , Fosfoproteínas/isolamento & purificação , Fosforilação , Fosfotransferases (Aceptor do Grupo Álcool)/efeitos dos fármacos , Fosfotirosina , Ratos , Valores de Referência , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Epinephrine is known to produce insulin resistance, but the exact molecular mechanism involved is unknown. In the present study we have examined the levels and phosphorylation state of the insulin receptor and of insulin receptor substrate 1 (IRS-1), as well as the association between IRS-1 and phosphatidylinositol 3-kinase (PI 3-kinase) in the liver and muscle of rats treated with epinephrine. The results demonstrate a decrease in insulin-stimulated receptor and IRS-1 phosphorylation levels which was accompanied by a reduction in the association of IRS-1 with PI 3-kinasein vivo in liver and muscle of epinephrine treated rats. These data suggest that molecular post-receptor defects may explain some aspects of the insulin resistance induced by catecholamines.
