Veterans Affairs San Diego Healthcare System and Department of Medicine, University of California, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Mol Cell Endocrinol. 2010 Feb 5;315(1-2):153-8. doi: 10.1016/j.mce.2009.05.020. Epub 2009 Jun 6.
The involvement of the beta-isoform of glycogen synthase kinase (GSK-3) in glucose metabolism and insulin action was investigated in cultured human skeletal muscle cells. A 60% reduction in GSK-3beta protein expression was attained by treatment with siRNA; GSK-3alpha expression was unaltered. GSK-3beta knockdown did not influence total glycogen synthase (GS) activity, but increased the phosphorylation-dependent activity (fractional velocity-FV) in the basal state. Insulin responsiveness of GSFV was doubled by GSK-3beta knockdown (p<0.05). Basal rates of glucose uptake (GU) were not significantly influenced by GSK-3beta knockdown, while insulin stimulation of GU was increased. Improvements in insulin action on GS and GU did not involve changes in protein expression of either IRS-1 or Akt 1/2. Maximal insulin stimulation of phosphorylation of Akt was unaltered by GSK-3beta knockdown. Unlike GSK-3alpha, GSK-3beta directly regulates both GS activity in the absence of added insulin and through control of insulin action.
研究了糖原合酶激酶（GSK-3）的β同工酶在人骨骼肌细胞葡萄糖代谢和胰岛素作用中的作用。用 siRNA 处理可使 GSK-3β蛋白表达减少 60%；GSK-3α表达无变化。GSK-3β敲低不影响总糖原合酶（GS）活性，但增加基础状态下磷酸化依赖性活性（分数速度-FV）。GSKF 的胰岛素反应性通过 GSK-3β敲低增加了一倍（p<0.05）。GSK-3β敲低对基础葡萄糖摄取（GU）率没有显著影响，而胰岛素刺激 GU 增加。胰岛素对 GS 和 GU 的作用改善不涉及 IRS-1 或 Akt 1/2 的蛋白表达变化。GSK-3β敲低不改变 Akt 的磷酸化的最大胰岛素刺激作用。与 GSK-3α不同，GSK-3β可直接调节无外加胰岛素时 GS 的活性和通过控制胰岛素作用。
