A role for the serine/threonine kinase, Akt, in insulin-stimulated glucose uptake.
A role for the serine/threonine kinase, Akt, in insulin-stimulated glucose uptake.
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DOI：
10.1042/bst0250981
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发表时间：
1997-08
影响因子：
3.9
通讯作者：
S. Summers;M. Birnbaum
中科院分区：
文献类型：
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作者：
S. Summers;M. Birnbaum
982大多数葡萄糖摄取的增加是由胰岛素引起的（图1）[1]。此外，胰岛素还诱导普遍表达的葡萄糖转运蛋白GLUT 1的质膜水平增加3-5倍，该转运蛋白在肌肉和脂肪组织中以相对较低的水平存在[Z]。尽管受到了相当多的关注，但将胰岛素到达细胞表面与其无数代谢功能（特别是其刺激GLUT 4易位）联系起来的分子事件尚未完全了解。胰岛素通过最初与其受体结合，激活后者的内在蛋白激酶活性来刺激细胞内反应[3]。活化的受体催化受体本身以及“接头”蛋白上的酪氨酸残基的磷酸化;两者都用于募集信号传导中间体。这种机制类似于其他各种生长因子所利用的机制。尽管如此，一些证据支持胰岛素受体酪氨酸激酶对胰岛素刺激GLUT 4易位至关重要的观点：（1）受体突变的患者显示胰岛素抵抗[4];（2）转染到大鼠脂肪细胞中的酪氨酸激酶缺陷型受体不能传递增加葡萄糖摄取的信号[5];（3）3 T3-L1脂肪细胞中微量注射抗胰岛素受体抗体阻断胰岛素刺激的GLUT 4易位（S. F.
982 most of the increase in glucose uptake initiated by insulin (Figure 1)[l]. In addition, insulin also induces a smaller, 3-5-fold increase in plasmamembrane levels of the ubiquitously expressed glucose transporter GLUT1 which is present in relatively low levels in muscle and adipose tissue [Z]. Despite considerable attention, the molecular events linking insulin’s arrival at the cell surface to its myriad metabolic functions, particularly its stimulation of GLUT4 translocation, are not fully understood. Insulin stimulates intracellular responses by initially binding to its receptor, activating the latter’s intrinsic protein kinase activity [3]. The activated receptor catalyses the phosphorylation of tyrosine residues on the receptor itself as well as ‘adaptor’proteins; both serve to recruit signalling intermediates. This mechanism is similar to that utilized by a variety of other growth factors. Nonetheless, several pieces of evidence support the notion that the insulin receptor tyrosine kinase is critical for insulin stimulation of GLUT4 translocation:(1) patients with mutations in the receptor display insulin resistance [4];(2) tyrosine kinase-deficient receptors transfected into rat adipocytes are incapable of transmitting the signal for increased glucose uptake [5];(3) anti-(insulin receptor) antibodies microinjected into 3T3-Ll adipocytes block insulinstimulated GLUT4 translocation (S. F.