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

Abstract:

:Insulin stimulates rapid tyrosine phosphorylation of the protein Shc, which subsequently binds to Grb2, resulting in the activation of a complex mitogenic signaling network. In this study, we examined the levels of Shc protein, its phosphorylation state and Shc-Grb2 association in liver, muscle and adipose tissue before and after insulin administration in three animal models of insulin resistance (chronic dexamethasone treatment, 72-h starvation and aging). There were no differences in Shc protein expression between tissues 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 hyperinsulinemic rats and in liver, muscle and adipose tissue of hyperinsulinemic 20-month-old rats. Alterations in Shc phosphorylation correlated well with the level of Shc-Grb2 association. These results indicate that Shc tyrosyl phosphorylation and Shc-Grb2 association are regulated in the different types of insulin resistance and that this regulation is apparently related to the animals' plasma insulin levels. The Shc-Grb2 association is directly related to the insulin-induced tyrosyl phosphorylation of Shc.

journal_name

Mol Cell Endocrinol

authors

Páez-Espinosa EV,Rocha EM,Velloso LA,Boschero AC,Saad MJ

doi

10.1016/s0303-7207(99)00137-9

keywords:

subject

Has Abstract

pub_date

1999-10-25 00:00:00

pages

121-9

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(99)00137-9

journal_volume

156

pub_type

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