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  • Title: IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance.
    Author: Murata Y, Tsuruzoe K, Kawashima J, Furukawa N, Kondo T, Motoshima H, Igata M, Taketa K, Sasaki K, Kishikawa H, Kahn CR, Toyonaga T, Araki E.
    Journal: Biochem Biophys Res Commun; 2007 Dec 14; 364(2):301-7. PubMed ID: 17950694.
    Abstract:
    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-1 expression may not provide a beneficial impact on glucose homeostasis in vivo.
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