IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance
IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance
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DOI：
10.1016/j.bbrc.2007.10.007
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发表时间：
2007-12-14
影响因子：
3.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
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作者：
Murata, Yusuke;Tsuruzoe, Kaku;Araki, Eiichi
胰岛素受体底物-1（IRS-1）是胰岛素受体和IGF-1受体的主要底物。在这项研究中，我们建立了IRS-1转基因（IRS-1-Tg）小鼠表达的小鼠IRS-1基因启动子控制下的人IRS-1 cDNA。在IRS-1-Tg小鼠中，IRS-1 mRNA表达在几乎所有组织中显著增加，但其蛋白表达在非常有限的组织（附睾脂肪和骨骼肌）中增加。IRS-1-Tg小鼠表现出葡萄糖耐受不良和显著增大的附睾脂肪量，以及升高的血清TNF-α浓度。重要的是，IRS- 1-Tg小鼠肝脏中的胰岛素信号显著减弱，这可能有助于葡萄糖耐受不良。我们的研究结果表明，过量的IRS- I表达可能不会对体内葡萄糖稳态产生有益的影响。(C)2007年爱思唯尔公司All rights reserved.
Insulin receptor substrate-1 (IRS-1) is the major substrate of both the insulin receptor and the IGF-1 receptor. In this study, we created IRS-1 transgenic (IRS-1-Tg) mice which express human IRS-1 cDNA under control of the mouse IRS-1 gene promoter. In the IRS-1-Tg mice, IRS-1 mRNA expression was significantly increased in almost all tissues, but its protein expression was increased in very limited tissues (epididymal fat and skeletal muscle). IRS-1-Tg mice showed glucose intolerance and significantly enlarged epididymal fat mass, as well as elevated serum TNF-alpha concentrations. Importantly insulin signaling was significantly attenuated in the liver of IRS- 1-Tg mice, which may contribute to the glucose intolerance. Our results suggest that excess IRS- I expression may not provide a beneficial impact on glucose homeostasis in vivo. (C) 2007 Elsevier Inc. All rights reserved.