AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells
AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells
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DOI：
10.1016/j.bbrc.2005.01.004
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发表时间：
2005-03-11
影响因子：
3.1
通讯作者：
Araki, E
中科院分区：
文献类型：
--
作者：
Nakamaru, K;Matsumoto, K;Araki, E
肝脏是胰岛素的主要靶器官之一，其胰岛素受体表达丰富。我们分析了AMPK激活剂AICAR对人肝癌细胞系HepG 2细胞中胰岛素受体表达的影响。AICAR处理48 h以剂量依赖性方式显著降低胰岛素受体蛋白的表达，然而，在3 T3-L1脂肪细胞或CHO细胞中未观察到AICAR的这种相同作用。AICAR处理后胰岛素受体mRNA的表达也降低。此外，胰岛素受体基因启动子的转录活性与荧光素酶试验研究下调AICAR治疗。腺苷转运体抑制剂双嘧达莫和腺苷激酶抑制剂5 '-氨基-5'-脱氧腺苷阻断AICAR对胰岛素受体蛋白、mRNA和启动子活性下调的作用。我们的研究结果表明，第一次，AMPK激活可以减少胰岛素受体的表达，至少部分，通过下调转录水平，这种效果可能是肝脏特异性的。(C)2005年爱思唯尔公司All rights reserved.
The liver is one of the major target organs of insulin in which the expression of insulin receptor is abundant. We analyzed the effect of AICAR, an AMPK activator, on the expression of insulin receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48 h significantly decreased the expression of the insulin receptor protein in a dose-dependent manner, however, this same effect of AICAR was not observed in either 3T3-L1 adipocytes or CHO cells. The expression of insulin receptor mRNA also decreased after AICAR treatment. In addition, the transcriptional activity of the insulin receptor gene promoter investigated with a luciferase assay was down-regulated by AICAR treatment. Dipyridamole, an adenosine transporter inhibitor, and 5'-amino-5'-deoxvadenosine, an adenosine kinase inhibitor, blocked the effect of AICAR on the down-regulation of the insulin receptor protein, mRNA, and promoter activity. Our findings suggest, for the first time, that AMPK activation could reduce the expression of insulin receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific. (C) 2005 Elsevier Inc. All rights reserved.