RESUMO
In this study, we demonstrate that pretreatment with aspirin inhibits GH-induced insulin resistance. GH was observed to lead to serine phosphorylation of IRS-1, a phenomenon which was reversed by aspirin in liver, muscle and WAT in parallel with a reduction in JNK activity. In addition, our data show an impairment of insulin activation in the IR/IRS/PI(3)kinase pathway and a reduction in IRS-1 protein levels in rats treated with GH, which was also reversed in the animals pretreated with aspirin. Overall, these results provide new insights into the mechanism of GH-induced insulin resistance.
Assuntos
Aspirina/farmacologia , Hormônio do Crescimento/farmacologia , Fosfoproteínas/metabolismo , Fosfosserina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Insulina/farmacologia , Proteínas Substratos do Receptor de Insulina , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculos/efeitos dos fármacos , Músculos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ratos , Ratos Wistar , Receptor de Insulina/metabolismoRESUMO
Whole body insulin resistance has been demonstrated in septic patients and in infected animals. In this study, we demonstrate that sepsis induces insulin resistance and that pretreatment with aspirin inhibits sepsis-induced insulin resistance. Sepsis was observed to lead to serine phosphorylation of IRS-1, a phenomenon which was reversed by aspirin in muscle and WAT, in parallel with a reduction in JNK activity. In addition, our data show an impairment of insulin activation of IR and IRS-1 tyrosine phosphorylation in septic rats and, consistent with the reduction of IRS-1 serine phosphorylation observed in septic animals pretreated with aspirin, there was an increase in IRS-1 protein levels and tyrosine phosphorylation in muscle and WAT. Overall, these results provide important new insights into the mechanism of sepsis-induced insulin resistance.