Insulin-induced tyrosine phosphorylation of Shc in liver, muscle and adipose tissue of insulin resistant rats

Insulin stimulates rapid tyrosine phosphorylation of the protein Shc, which subsequently binds to Grb2, resulting in the activation of a complex mitog enic signaling network. In this study, we examined the levels of Shc protei n, its phosphorylation state and Shc-Grb2 association in liver, muscle and adipose tissue before and after insulin administration in three animal mode ls of insulin resistance (chronic dexamethasone treatment, 72-h starvation and aging). There were no differences in Shc protein expression between tis sues from control and insulin resistant animals. In fasted hypoinsulinemic rats, there was a decrease in insulin-induced Shc phosphorylation in liver and adipose tissue.:However, a significant increase in Shc phosphorylation was observed in liver and muscle from dexamethasone-treated hyperinsulinemi c rats and in liver, muscle and adipose tissue of hyperinsulinemic 20-month -old rats. Alterations in Shc phosphorylation correlated well with the leve l of Shc-Grb2 association. These results indicate that Shc tyrosyl phosphor ylation and Shc-Grb2 association are regulated in the different types of in sulin resistance and that this regulation is apparently related to the anim als' plasma insulin levels. The Shc-Grb2 association is directly related to the insulin-induced tyrosyl phosphorylation of Shc. (C) 1999 Elsevier Scie nce Ireland Ltd. All rights reserved.