Insulin-induced tyrosine phosphorylation of Shc in liver, muscle and adipose tissue of insulin resistant rats
Insulin-induced tyrosine phosphorylation of Shc in liver, muscle and adipose tissue of insulin resistant rats
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DOI：
10.1016/s0303-7207(99)00137-9
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发表时间：
1999-10-25
影响因子：
4.1
通讯作者：
Saad, MJA
中科院分区：
文献类型：
--
作者：
Páez-Espinosa, EV;Rocha, EM;Saad, MJA
胰岛素刺激蛋白Shc的快速酪氨酸磷酸化，随后与Grb 2结合，导致复杂的促有丝分裂信号网络的激活。在这项研究中，我们研究了Shc蛋白的水平，其磷酸化状态和Shc-Grb 2协会在肝脏，肌肉和脂肪组织之前和之后的胰岛素给药在三种动物模型的胰岛素抵抗（慢性地塞米松治疗，72小时饥饿和老化）。对照组和胰岛素抵抗动物的组织中Shc蛋白表达无差异。在禁食低胰岛素血症大鼠中，肝脏和脂肪组织中胰岛素诱导的Shc磷酸化减少。然而，在地塞米松治疗的高胰岛素血症大鼠的肝脏和肌肉以及高胰岛素血症20月龄大鼠的肝脏、肌肉和脂肪组织中观察到Shc磷酸化显著增加。Shc磷酸化的改变与Shc-Grb 2相关水平密切相关。这些结果表明，Shc酪氨酰磷酸化和Shc-Grb 2缔合在不同类型的胰岛素抵抗中受到调节，并且这种调节显然与动物的血浆胰岛素水平相关。Shc-Grb 2的结合与胰岛素诱导的Shc酪氨酰磷酸化直接相关。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
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. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.