Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport
Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport
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DOI：
10.1139/h07-026
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Wojtaszewski, Jorgen F. P.
中科院分区：
文献类型：
--
作者：
Cartee, Gregory D.;Wojtaszewski, Jorgen F. P.
胰岛素和运动是增加骨骼肌葡萄糖转运的最重要的生理刺激，可触发GLUT4葡萄糖转运蛋白从细胞内部到细胞表面的重新分布，从而增加葡萄糖的转运能力。与GLUT4易位相关的最远端的胰岛素信号蛋白Akt底物160 kDa(AS160)在胰岛素刺激的3T3-L1脂肪细胞中被磷酸化，这对胰岛素刺激的GLUT4易位和葡萄糖运输是重要的。胰岛素还可诱导骨骼肌中AS160磷酸化的快速增加，且呈剂量依赖性。来自骨骼肌的现有数据支持在脂肪细胞中发展的关于AS160在调节胰岛素刺激的葡萄糖运输中所起作用的概念。体内运动、体外收缩或原位收缩也可以刺激AS160的磷酸化。AMP激活的蛋白激酶(AMPK)可能在运动/收缩反应中对AS160的磷酸化起重要作用，而Akt2在胰岛素刺激的肌肉中对AS160的磷酸化似乎是重要的。AS160在运动/收缩刺激的葡萄糖摄取中起作用的证据目前还没有定论。由胰岛素和运动/收缩刺激的不同信号通路在AS160会聚。尽管AS160的磷酸化显然对胰岛素刺激的GLUT4转位和葡萄糖运输很重要，但目前还不确定AS160的磷酸化水平升高是否与运动/收缩具有类似的作用。
Insulin and exercise, the most important physiological stimuli to increase glucose transport in skeletal muscle, trigger a redistribution of GLUT4 glucose transporter proteins from the cell interior to the cell surface, thereby increasing glucose transport capacity. The most distal insulin signaling protein that has been linked to GLUT4 translocation, Akt substrate of 160 kDa (AS160), becomes phosphorylated in insulin-stimulated 3T3-L1 adipocytes; this is important for insulin-stimulated GLUT4 translocation and glucose transport. Insulin also induces a rapid and dose-dependent increase in AS160 phosphorylation in skeletal muscle. Available data from skeletal muscle support the concepts developed in adipocytes with regard to the role AS160 plays in the regulation of insulin-stimulated glucose transport. In vivo exercise, in vitro contractions, or in situ contractions can also stimulate AS160 phosphorylation. AMP-activated protein kinase (AMPK) is likely important for phosphorylating AS160 in response to exercise/contractile activity, whereas Akt2 appears to be important for insulin-stimulated AS 160 phosphorylation in muscle. Evidence of a role for AS160 in exercise/contraction-stimulated glucose uptake is currently inconclusive. The distinct signaling pathways that are Stimulated by insulin and exercise/contraction converge at AS160. Although AS160 phosphorylation is apparently important for insulin-stimulated GLUT4 translocation and glucose transport, it is uncertain whether elevated AS160 phosphorylation plays a similar role with exercise/contraction.