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蛋白质AS160/TBC1D4在葡萄糖转运至骨骼肌过程中的作用

[The role of protein AS160/TBC1D4 in the transport of glucose into skeletal muscles].

作者信息

Mikłosz Agnieszka, Konstantynowicz Karolina, Stepek Tomasz, Chabowski Adrian

机构信息

Zakład Fizjologii Uniwersytetu Medycznego w Białymstoku.

出版信息

Postepy Hig Med Dosw (Online). 2011 May 6;65:270-6. doi: 10.5604/17322693.941635.

Abstract

Skeletal muscle plays an essential role in the regulation of whole-body glucose homeostasis. Glucose is transported into the muscle cells via protein-mediated transport that requires sarcolemmal glucose transporters (GLUT). Translocation of GLUT-4 to the plasma membranes is the most potent factor stimulating glucose uptake by myocytes. Relocation of GLUT-4 from an intracellular pool(s) to the plasma membranes is activated by either insulin (associated with activation of kinase PI3K), or physical activity (associated with activation of kinase AMPK). Recent studies have shown that the signaling protein known as AS160 is involved in the directed GLUT-4 intramyocellular redistribution. AS160 protein appears to be activated by the insulin pathway as well as by AMPK. Moreover, in human skeletal muscles that are insulin-resistant, insulin-stimulated phosphorylation of AS160 is significantly impaired. Therefore, decreased insulin-induced AS160 phosphorylation that results in diminished GLUT-4 redistribution to the plasma membrane may play an important role in insulin resistance in vivo.

摘要

骨骼肌在全身葡萄糖稳态调节中起关键作用。葡萄糖通过蛋白质介导的转运进入肌肉细胞,这一过程需要肌膜葡萄糖转运蛋白(GLUT)。GLUT-4向质膜的转位是刺激心肌细胞摄取葡萄糖的最有效因素。GLUT-4从细胞内池重新定位到质膜,可由胰岛素(与激酶PI3K的激活相关)或体力活动(与激酶AMPK的激活相关)激活。最近的研究表明,被称为AS160的信号蛋白参与了GLUT-4在细胞内的定向重新分布。AS160蛋白似乎可被胰岛素途径以及AMPK激活。此外,在胰岛素抵抗的人体骨骼肌中,胰岛素刺激的AS160磷酸化显著受损。因此,胰岛素诱导的AS160磷酸化减少导致GLUT-重新分布到质膜减少,这可能在体内胰岛素抵抗中起重要作用。

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