Crucial role of the small GTPase Rac1 in insulin‐stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma
Crucial role of the small GTPase Rac1 in insulin‐stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma
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DOI：
10.1096/fj.09-137380
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发表时间：
2010-07
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通讯作者：
Shuji Ueda;S. Kitazawa;K. Ishida;Yuki Nishikawa;M. Matsui;H. Matsumoto;T. Aoki;Shinsuke Nozaki;T. Takeda;Y. Tamori;A. Aiba;C. Kahn;T. Kataoka;T. Satoh
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作者：
Shuji Ueda;S. Kitazawa;K. Ishida;Yuki Nishikawa;M. Matsui;H. Matsumoto;T. Aoki;Shinsuke Nozaki;T. Takeda;Y. Tamori;A. Aiba;C. Kahn;T. Kataoka;T. Satoh
Rho家族GTCRac 1参与成肌细胞系中葡萄糖摄取的调节。然而，没有证据表明Rac 1的作用已经提供了一个小鼠模型。本研究的目的是测试Rac 1参与小鼠骨骼肌中的胰岛素作用。静脉注射胰岛素确实引起腓肠肌中Rac 1的激活，表明Rac 1参与了该信号通路。然后，我们研究了胰岛素刺激的促进性葡萄糖转运蛋白GLUT 4从其储存位点转移到骨骼肌肌膜是否依赖于Rac 1。我们发现，组成性激活的Rac 1的异位表达，以及静脉注射胰岛素，导致GLUT 4易位到腓肠肌肌膜，如瞬时表达的外表面表位标记的GLUT 4报告基因的免疫荧光染色所示。特别值得注意的是，与对照小鼠相比，骨骼肌特异性rac 1敲除小鼠中胰岛素依赖性但非组成性激活的rac 1诱导的GLUT 4易位显著受到抑制。内源性GLUT 4的免疫金电子显微镜分析得到了类似的结果。总的来说，我们提出了Rac 1在胰岛素依赖性GLUT 4易位到骨骼肌肌膜中的关键作用，迄今为止仅通过细胞培养研究预测。上田，S.，Kitazawa，S.，Ishida，K，Nishikawa，Y.，Matsui，M.，松本，H.，青木，T.，Nozaki，S.，Takeda，T.，Tamori，Y.，Aiba，A.，卡恩角R.，Kataoka，T.，Satoh，T.小GT3 Rac 1在胰岛素刺激的葡萄糖转运蛋白4转运至小鼠骨骼肌肌膜中的关键作用FASEB J.24，2254-2261（2010）。www.fasebj.org
The Rho family GTPase Rac1 has been implicated in the regulation of glucose uptake in myoblast cell lines. However, no evidence for the role of Rac1 has been provided by a mouse model. The purpose of this study is to test the involvement of Rac1 in insulin action in mouse skeletal muscle. Intravenous administration of insulin indeed elicited Rac1 activation in gastrocnemius muscle, suggesting the involvement of Rac1 in this signaling pathway. We then examined whether insulin‐stimulated translocation of the facilitative glucose transporter GLUT4 from its storage sites to the skeletal muscle sarcolemma depends on Rac1. We show that ectopic expression of constitutively activated Rac1, as well as intravenous administration of insulin, caused translocation of GLUT4 to the gastrocnemius muscle sarcolemma, as revealed by immunofluorescent staining of a transiently expressed exofacial epitope‐tagged GLUT4 reporter. Of particular note, insulin‐dependent, but not constitutively activated Rac1‐induced, GLUT4 translocation was markedly suppressed in skeletal muscle‐specific rac1‐knockout mice compared to control mice. Immunogold electron microscopic analysis of endogenous GLUT4 gave similar results. Collectively, we propose a critical role of Rac1 in insulin‐dependent GLUT4 translocation to the skeletal muscle sarcolemma, which has heretofore been predicted solely by cell culture studies.—Ueda, S., Kitazawa, S., Ishida, K, Nishikawa, Y., Matsui, M., Matsumoto, H., Aoki, T., Nozaki, S., Takeda, T., Tamori, Y., Aiba, A., Kahn, C. R., Kataoka, T., Satoh, T. Crucial role of the small GTPase Rac1 in insulinstimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma. FASEB J. 24, 2254–2261 (2010). www.fasebj.org