2010 Fiscal Year Final Research Report
Molecular mechanisms of Insulin signal transduction and diabetes mellitus
Project/Area Number |
20390095
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathological medical chemistry
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Research Institution | The University of Tokushima |
Principal Investigator |
EBINA Yousuke The University of Tokushima, 疾患酵素学研究センター, 教授 (00112227)
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Co-Investigator(Renkei-kenkyūsha) |
UCHIYAMA Keiji 徳島大学, 疾患酵素学研究センター, 准教授 (60294039)
YUASA Tomoyuki 徳島大学, 疾患酵素学研究センター, 准教授 (50304556)
NAGAYA Hisao 徳島大学, 疾患酵素学研究センター, 助教 (60464343)
OGURA Yuko 徳島大学, 疾患酵素学研究センター, 研究員 (90464354)
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Project Period (FY) |
2008 – 2010
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Keywords | 分子病態学 / インスリンシグナル伝達 |
Research Abstract |
Akt substrate of 160kDa (AS160) is a Rab GTPase activating protein (GAP) and was recently identified as a component of the insulin signaling pathway of glucose transporter type 4 (GLUT4) translocation. We and others, previously reported that the activation of Galphaq protein-coupled receptors (GalphaqPCRs) also stimulated GLUT4 translocation and glucose uptake in several cell lines. Here, we report that the activation of GalphaqPCRs also promoted phosphorylation of AS160 by the 5'-AMP activated proteinkinase (AMPK). Rat 3Y1 cells lacking AS160 did not show insulin-induced GLUT4 translocation. The cells stably expressing GLUT4 revealed GLUT4 vesicles that were mainly localized in the perinuclear region and less frequently on the cell surface. After expression of exogenous AS160, GLUT4 on the cell surface decreased and GLUT4 vesicles were redistributed throughout the cytoplasm. Although PMA-induced or sodium fluoride-induced GLUT4 translocation was significantly increased in these cells, insulin did not affect GLUT4 translocation. These results suggest that AS160 is a common regulator of insulin-and GalphaqPCR activation-mediated GLUT4 distribution in the cells.
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Research Products
(9 results)
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[Journal Article] The Rab GTPase-Activating Protein AS160 as A Common Regulator of Insulin- and Gq-Mediated Intracellular GLUT4 Vesicle DistributionA2009
Author(s)
Yuasa Tomoyuki, Uchiyama Keiji, Yuko OGURA, Kimura Masafumi, Kiyoshi TESHIGAWARA, Hosaka Toshio, Yoshinori TANAKA, Obata Toshiyuki, Hiroyuki SANO, Kishi Kazuhiro, Ebina Yousuke
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Journal Title
Endocrine Journal Vol.56, No.3
Pages: 345-359
Peer Reviewed
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[Presentation] Soluble insulin receptor ectodomain in the plasma is a possible broad-spectrum tumor marker2009
Author(s)
湯浅智之, 矢野聖二, 西岡安彦, 久保宜明, 高橋正幸, 中逵弘能, 長屋寿雄, 金山博臣, 荒瀬誠治, 曽根三郎, 蛯名洋介
Organizer
第68回 日本癌学会学術総会記事,pp.450-450
Place of Presentation
Yokohama
Year and Date
20091001-20091003
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[Presentation] 可溶性インスリン受容体細胞外ドメイン(sIRα)は高血糖に相関して血中濃度が高まる2009
Author(s)
湯浅智之, 小畑利之, 横田一郎, 岡本英治, 長屋寿雄, 橋田誠一, 前川聡, 柏木厚典, 松本満, 松本俊夫, 岸和弘, 蛯名洋介
Organizer
第7回1型糖尿病研究会
Place of Presentation
日光
Year and Date
2009-11-07
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[Presentation] 可溶化インスリン受容体細胞外ドメイン(sIR)は癌患者血清中で増加している2009
Author(s)
湯浅智之, 小畑利之, 矢野聖二, 岡本英治, 西岡安彦, 久保宜明, 高橋正幸, 中逵弘能, 長屋寿雄, 金山博臣, 荒瀬誠治, 曽根三郎, 蛯名洋介
Organizer
第29回日本分子腫瘍マーカー研究会
Place of Presentation
横浜
Year and Date
2009-09-30
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[Presentation] Soluble insulin receptor ectodomain is elevated in the plasma of patients with diabetes.2008
Author(s)
Yuasa Tomoyuki, Obata Toshiyuki, Yokota Ichiro, Okamoto Eiji, Kanezaki Yoshiko, Maegawa Hiroshi, Hirota Fumiko, Kishi Kazuhiro, Hashida Seiichi, Nagaya Hisao, Yuko Ogura, Kazuhiko Masuda, Matsumoto Mitsuru, Matsumoto Toshio, Kashiwagi Atsunori, Ebina Yousuke
Organizer
The 1st Insulin Resistance in Metabolic Disease Forum
Place of Presentation
Osaka
Year and Date
2008-08-20
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