title: IRS-1 transgenic mice show increased epididymal fat mass and insulin resistance.
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.
authors.affiliation: Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murata
authors.forename: Kaku
authors.initials: K
authors.lastname: Tsuruzoe
authors.forename: Junji
authors.initials: J
authors.lastname: Kawashima
authors.forename: Noboru
authors.initials: N
authors.lastname: Furukawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Motoshima
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Igata
authors.forename: Kayo
authors.initials: K
authors.lastname: Taketa
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Kishikawa
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Toyonaga
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D004822:Epididymis / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose