Role And Mechanisms Of Insulin Receptor Substrate 1 Serine～(307) On Insulin Resistance After Burn

Disordered glucose metabolism and insulin resistance were major metabolic abnormalities after burn. The exact molecular mechanism of insulin resistance has not been elucidated following thermal injury. We initiated this study based on the hypothesis that insulin resistance after burn in vivo is induced by IRS-1 Ser307 hyper-phosphorylation of IRS-1 and Ser307 integrates feedback and heterologpus signals to attenuate IRS-1-mediated signals and contribute to insulin resistance. Furthermore, mTOR and JNK may play a crucial role in mediating Ser307 hyper-phosphorylation of IRS-1 after burn. We used an animal model of a 30%TBSA full thickness third degree burn injury and confirmed that Severe thermal injury caused insulin resistance and resulted in significantly dynamic changes of abnormal glucose metabolism in vivo, which occurred on PBD1, peaked ion PBD3 and moderately alleviated on PBD10, but still remained abnormal on PBD14. Moreover, we also found Ser307 hyper-phosphorylation of IRS-1 may be one of molecular mechanisms of insulin resistance after burn and demonstrated mTOR is an important aspect of the signaling event that may mediate IRS-1 Ser307 phosphorylation and at least, partly contributes to burn-induced insulin resistance, whilst phosphorylation of IRS-1 Ser307 correlates with JNK activity. JNK signaling pathway plays a regulating role in abnormal insulin signaling transduction and insulin resistance following severe thermal injury.