IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance

• Published in: Biochemical and biophysical research communications Vol. 364; no. 2; pp. 301 - 307
• Main Authors: Murata, Yusuke, Tsuruzoe, Kaku, Kawashima, Junji, Furukawa, Noboru, Kondo, Tatsuya, Motoshima, Hiroyuki, Igata, Motoyuki, Taketa, Kayo, Sasaki, Kazunari, Kishikawa, Hideki, Kahn, C. Ronald, Toyonaga, Tetsushi, Araki, Eiichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-12-2007
• Subjects: Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Epididymis - metabolism; Epididymis - pathology; Glucose - metabolism; Glucose Intolerance - genetics; Glucose Intolerance - metabolism; Insulin Receptor Substrate Proteins; Insulin resistance; Insulin Resistance - physiology; IRS-1; Liver - metabolism; Male; Mice; Mice, Transgenic; Muscle, Skeletal - metabolism; Phosphoproteins - biosynthesis; Phosphoproteins - genetics; Promoter Regions, Genetic; RNA, Messenger - biosynthesis; TNF-α; Tumor Necrosis Factor-alpha - metabolism; TNF-α; IRS-1; Insulin resistance
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.10.007

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-α 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.