Cellular chromium enhances activation of insulin receptor kinase.
Cellular chromium enhances activation of insulin receptor kinase.
复制标题
细胞铬增强胰岛素受体激酶的激活。
DOI：
10.1021/bi0473152
复制
发表时间：
2005
期刊：
影响因子：
2.9
通讯作者：
Brautigan,DavidL
中科院分区：
文献类型：
--
作者：
Wang,Hong;Kruszewski,Allison;Brautigan,DavidL
Chromium has been recognized for decades as a nutritional factor that improves glucose tolerance by enhancing in vivo insulin action, but the molecular mechanism is unknown. Here we report pretreatment of CHO-IR cells with chromium enhances tyrosine phosphorylation of the insulin receptor. Different chromium(III) compounds were effective at enhancing insulin receptor phosphorylation in intact cells, but did not directly activate recombinant insulin receptor kinase. The level of insulin receptor phosphorylation in cells can be increased by inhibition of the opposing protein tyrosine phosphatase (PTP1B), a target for drug development. However, chromium did not inhibit recombinant human PTP1B using eitherp-nitrophenyl phosphate or the tyrosine-phosphorylated insulin receptor as the substrate. Chromium also did not alter reversible redox regulation of PTP1B. Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Plasma membranes prepared from chromium-treated cells had higher specific activity of insulin-dependent kinase relative to controls. We conclude that cellular chromium potentiates insulin signaling by increasing insulin receptor kinase activity, separate from inhibition of PTPase. Our results suggest that nutritional and pharmacological therapies may complement one another to combat insulin resistance, a hallmark of type 2 diabetes.
