Dephosphorylation increases insulin-stimulated receptor kinase activity in skeletal muscle of obese Zucker rats

被引：21

作者：

Zhou, Q ^{[1
]}

Dolan, PL ^{[1
]}

Dohm, GL ^{[1
]}

机构：

[1] E Carolina Univ, Sch Med, Dept Biochem, Greenville, NC 27858 USA

来源：

MOLECULAR AND CELLULAR BIOCHEMISTRY | 1999年 / 194卷 / 1-2期

关键词：

insulin resistance; skeletal muscle; serine threonine phosphorylation; insulin signaling; obesity; Zucker rats;

D O I：

10.1023/A:1006942831223

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Serine/threonine phosphorylation of insulin receptor has been implicated in the development of insulin resistance. To investigate whether dephosphorylation of serine/threonine residues of the insulin receptor may restore the decreased insulin-stimulated receptor tyrosine kinase activity in skeletal muscle of obese Zucker rats, insulin receptor tyrosine kinase activity was measured before and after alkaline phosphatase treatment. Compared to lean controls, insulin-stimulated glucose transport was depressed by 61% (p < 0.05) in obese Zucker rats. The insulin receptor and insulin receptor substrate-1 contents were decreased by 14% (p < 0.05) and 16% (p < 0.05), respectively, in skeletal muscle of obese Zucker rats. In vivo insulin-induced tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 was depressed by 82% (p < 0.05) and 86% (p < 0.05), respectively. In the meantime, in vitro insulin-stimulated receptor tyrosine kinase activity in obese rats was decreased by 39% (p < 0.05). Dephosphorylation of the insulin receptor by prior alkaline phosphatase treatment increased insulin-stimulated receptor tyrosine kinase activity in both lean and obese Zucker rats, but the increase was three times greater in obese Zucker rats (p < 0.05). These findings suggest that excessive serine/threonine phosphorylation of the insulin receptor in obese Zucker rats may be a cause for insulin resistance in skeletal muscle.

引用

页码：209 / 216

页数：8

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