2008 Fiscal Year Final Research Report
The roles of insulin receptor substrate-2 in the regulation of glucosehomeostasis and atherosclerosis
| Project/Area Number |
19591037
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUBOTA Naoto The University of Tokyo, 医学部・附属病院, 特任准教授 (50396719)
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| Co-Investigator(Renkei-kenkyūsha) |
KADOWAKI Takashi 東京大学, 医学部・附属病院, 教授 (30185889)
UEKI Kojiro 東京大学, 医学部・附属病院, 准教授 (00396714)
YAMAUCHI Toshimasa 東京大学, 医学部・附属病院, 特任准教授 (40372370)
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| Project Period (FY) |
2007 – 2008
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| Keywords | インスリン受容体基質-2 / 血管内皮細胞 / 糖代謝 / 動脈硬化症 |
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| Research Abstract |
2007年度に、血管内皮細胞において主要なIRS であるIRS-2 に着目し、インスリン抵抗性と血管内皮機能について、血管内皮細胞特異的IRS-2欠損マウス(ETIRS2KO マウス)を用いて検討を行った。その結果、血管内皮細胞におけるIRS-2欠損により血管内皮機能が低下し、インスリンによる骨格筋血流の増加や骨格筋間質へのインスリン移行の増加が障害され、その結果インスリン抵抗性を惹起した可能性が示唆された。そこで2008年度は、血管内皮機能改善薬をETIRS2KO マウスに投与し、骨格筋のインスリン抵抗性が改善するかどうかについて検討したところ、血管内皮機能改善薬の投与によりETIRS2KO では骨格筋血流や骨格筋間質のインスリン濃度の回復が認められ、骨格筋のインスリン抵抗性が改善した。
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[Journal Article] AdiponectinSuppresses Colorectal Carcinogenesis under the High-fat Diet Condition2008
Author(s)
Fujisawa T, Endo H, Tomimoto A, SugiyamaM, Takahashi H, Saito S, Inamori M,Nakajima N, Watanabe M, Kubota N,Yamauchi T, Kadowaki T, Wada K,Nakagama H, Nakajima A.
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Journal Title
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[Journal Article] TamaokiN, Nomura T, Kosaka K. An Efficient reproductive method for Irs2-/- micewith C57BL/6JJcl genetic background2008
Author(s)
Hashimoto H, Eto T, Kamisako T, Hoya N,Hatakeyama T, Arai T, Yokosuka M,Ohnishi Y, Ito M, Hioki K, Suzuki R,Ohsugi M, Saito M, Ueyama Y, YamauchiT, Kubota N, Tobe K, Kadowaki T.
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Journal Title
Exp. Anim. 57
Pages: 407-411
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[Journal Article] Yamauchi T, Tobe K, Kadowaki T, KosakaK. Fulminant type 1 diabetes mellitusobserved in insulin receptor substrate2 deficient mice.2008
Author(s)
Arai T, Hashimoto H, Kawai K, Mori A,Ohnishi Y, Hioki K, Ito M, Saito M,Ueyama Y, Ohsugi M, Suzuki R, Kubota N.
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Journal Title
Clin. Exp. Med. 8
Pages: 93-99
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[Journal Article] Dynamic functional relay between insulin receptorsubstrate 1 and 2 in hepatic insulinsignaling during fasting and feeding2008
Author(s)
Kubota N, Kubota T, Itoh S, Kumagai H, Kozono H, Takamoto I, Mineyama T, OgataH, Tokuyama K, Ohsugi M, Sasako T, MoroiM, Sugi K, Kakuta S, Iwakura Y, Noda T,Ohnishi S, Nagai R, Tobe K, Terauchi Y,Ueki K, Kadowaki T.
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Journal Title
Cell Metab. 8
Pages: 49-64
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[Journal Article] Molecular mechanismof moderate insulin resistance in adiponectin-knockout mice2008
Author(s)
Yano W, Kubota N, Itoh S, Kubota T, Awazawa M, Moroi M, Sugi K, Takamoto I, Ogata H, Tokuyama K, Noda T, Terauchi Y, Ueki K, Kadowaki T.
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Journal Title
Endocr. J. 55
Pages: 515-522
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[Journal Article] Peroxisomeproliferator-activated receptor gamma(PPARgamma) suppresses colonic epithelial cell turnover and coloncarcinogenesis through inhibition ofthe beta-catenin/T cell factor (TCF)pathway2008
Author(s)
Fujisawa T, Nakajima A, Fujisawa N, Takahashi H, Ikeda I, Tomimoto A,Yonemitsu K, Nakajima N, Kudo C, Wada K, Kubota N, Terauchi Y, Kadowaki T, Nakagama H, Blumberg RS
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Journal Title
J. Pharmacol. Sci. 106
Pages: 627-638
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[Journal Article] Adiponectin induces insulinsecretion in vitro and in vivo at a lowglucose concentration.2008
Author(s)
Okamoto M, Ohara-Imaizumi M, Kubota N, Hashimoto S, Eto K, Kanno T, Kubota T,Wakui M, Nagai R, Noda M, Nagamatsu S,Kadowaki T
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Journal Title
Diabetologia 51
Pages: 827-835
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[Journal Article] Role of alteredrenal lipid metabolism in thedevelopment of renal injury induced bya high-fat diet2007
Author(s)
Kume S, Uzu T, Araki S, Sugimoto T,Isshiki K, Chin-Kanasaki M, Sakaguchi M,Kubota N, Terauchi Y, Kadowaki T, HanedaM, Kashiwagi A, Koya D
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Journal Title
J. Am. Soc. Nephrol 18
Pages: 2715-2723
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[Journal Article] Adiponectin Stimulates AMP-ActivatedProtein Kinase in the Hypothalamus andIncreases Food Intake.2007
Author(s)
Kubota N, Yano W, Kubota T, YamauchiT, Itoh S, Kumagai H, Kozono H, TakamotoI, Okamoto S, Shiuchi T, Suzuki R, SatohH, Tsuchida A, Moroi M, Sugi K, Noda T,Ebinuma H, Ueta Y, Kondo T, Araki E,Ezaki O, Nagai R, Tobe K, Terauchi Y,Ueki K, Minokoshi Y, Kadowaki T
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Journal Title
Cell Metab 6
Pages: 55-68
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