ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells
ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells
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DOI：
10.1016/j.yexcr.2005.04.028
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发表时间：
2005-08-15
影响因子：
3.7
通讯作者：
Tamaki, T
中科院分区：
文献类型：
--
作者：
Izawa, Y;Yoshizumi, M;Tamaki, T
临床证据提示高血压与胰岛素抵抗有关，血管紧张素II （Ang II）与胰岛素信号通路之间可能发生串扰。我们现在报道Ang II对胰岛素诱导的葡萄糖摄取的影响及其在血管平滑肌细胞（VSMC）中的细胞内机制。我们检测了大鼠主动脉平滑肌细胞（RASMC）中葡萄糖转运蛋白-4 （GLUT-4）的易位和葡萄糖摄取。采用免疫沉淀和免疫印迹法检测丝裂原活化蛋白（MAP）激酶和Akt活性，以及胰岛素受体底物-1 （IRS-1）在丝氨酸和酪氨酸残基上的磷酸化水平。因此，Ang II抑制了胰岛素诱导的glut4在RASMC中从细胞质到质膜的易位。Ang II诱导细胞外信号调节激酶（ERK） 1/2和c-Jun n末端激酶（JNK）激活和IRS-1在Ser（307）和Ser（616）上的磷酸化。Ang ii诱导的IRS-1的Ser（307）和Ser（616）磷酸化被MEK抑制剂PD98059和JNK抑制剂SP600125抑制。胰岛素刺激的IRS-1酪氨酸磷酸化和Akt活化的Ang II抑制被PD98059逆转，而SP600125则没有。Ang II抑制胰岛素诱导的葡萄糖摄取，PD98059也能逆转这一作用，而SP600125则不能。研究表明，Ang ii诱导的ERK1/2激活通过ras -1的丝氨酸磷酸化抑制胰岛素依赖性葡萄糖摄取。(c) 2005爱思唯尔公司版权所有。
Clinical evidence suggests a relationship between hypertension and insulin resistance, and cross-talk between angiotensin II (Ang II) and insulin signaling pathways may take place. We now report the effect of Ang II on insulin-induced glucose uptake and its intracellular mechanisms in vascular smooth Muscle cells (VSMC). We examined the translocation of glucose transporter-4 (GLUT-4) and glucose uptake in rat aortic smooth muscle cells (RASMC). Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. As a result, Ang II inhibited insulin-induced GLUT-4 translocation from cytoplasm to the plasma membrane in RASMC. Ang II induced extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation and IRS-1 phosphorylation at Ser(307) and Ser(616). Ang II-induced Ser(307) and Ser(616) phophorylation of IRS-1 was inhibited by a MEK inhibitor, PD98059, and a JNK inhibitor, SP600125. Ang II inhibition of insulin-stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125. Ang II inhibited insulin-induced glucose uptake, which was also reversed by PD98059 but not by SP600125. It is shown that Ang II-induced ERK1/2 activation inhibits insulin-dependent glucose uptake through serine phophorylation of IRS-1 in RASMC. (c) 2005 Elsevier Inc. All rights reserved.