Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.
Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.
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胰岛素受体底物 1 独立胰岛素信号传导通路介导胰岛素反应性葡萄糖转运蛋白 (GLUT4) 易位的证据。
DOI：
10.1073/pnas.93.16.8401
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发表时间：
1996
影响因子：
11.1
通讯作者：
Olefsky,JM
中科院分区：
文献类型：
--
作者：
Morris,AJ;Martin,SS;Haruta,T;Nelson,JG;Vollenweider,P;Gustafson,TA;Mueckler,M;Rose,DW;Olefsky,JM
激活的胰岛素受体（IR）与其底物胰岛素受体底物1（IRS-1）通过IRS-1的磷酸酪氨酸结合结构域和以IR的磷酸酪氨酸960为中心的NPXY基序相互作用，对IRS-1的磷酸化是重要的。我们研究了这种相互作用在刺激葡萄糖转运的胰岛素信号通路中的作用。利用3 T3-L1脂肪细胞中的竞争性抑制剂的显微注射，我们已经发现，IR/IRS-1相互作用的中断后，胰岛素响应性葡萄糖转运蛋白（GLUT 4）的易位没有影响。这些试剂的活性通过其阻断3 T3-L1脂肪细胞和胰岛素应答大鼠1成纤维细胞中两种不同胰岛素生物效应（膜皱褶和有丝分裂）的胰岛素刺激的能力来证明。这些数据表明，磷酸化IRS-1不是导致GLUT 4易位的代谢胰岛素信号通路的重要组成部分，但它似乎是其他胰岛素生物效应所必需的。
Interaction of the activated insulin receptor (IR) with its substrate, insulin receptor substrate 1 (IRS-1), via the phosphotyrosine binding domain of IRS-1 and the NPXY motif centered at phosphotyrosine 960 of the IR, is important for IRS-1 phosphorylation. We investigated the role of this interaction in the insulin signaling pathway that stimulates glucose transport. Utilizing microinjection of competitive inhibitory reagents in 3T3-L1 adipocytes, we have found that disruption of the IR/IRS-1 interaction has no effect upon translocation of the insulin-responsive glucose transporter (GLUT4). The activity of these reagents was demonstrated by their ability to block insulin stimulation of two distinct insulin bioeffects, membrane ruffling and mitogenesis, in 3T3-L1 adipocytes and insulin-responsive rat 1 fibroblasts. These data suggest that phosphorylated IRS-1 is not an essential component of the metabolic insulin signaling pathway that leads to GLUT4 translocation, yet it appears to be required for other insulin bioeffects.