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Induction of IGF-I production by amino acids in the liver : Its significance in the cirrhotic liver

Research Project

Project/Area Number 20590761
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

TOMIYA Tomoaki  The University of Tokyo, 医学部附属病院, 特任講師 (90227637)

Co-Investigator(Kenkyū-buntansha) IKEDA Hitoshi  東京大学, 医学部附属病院, 准教授 (80202422)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords再生医学 / 栄養学 / 内科 / トランスレイショナルリサーチ / トランスレーショナルリサーチ / 生理活性
Research Abstract

Insulin-like growth factor I (IGF-I) plays an important role in growth, metabolism, survival and oxidative stress of various types of cells. IGF-I is produced predominantly by the liver, especially by hepatocytes. Serum IGF-I levels are decreased in patients with liver cirrhosis. Supplementation of IGF-I induces the improvement of liver function in patients with liver cirrhosis. In this study, we examined stimulatory effect of amino acids on IGF-I production by hepatocytes, and the effect of IGF-I on hepatocyte growth and function to investigate the possibility that amino acid administration improves liver function in patients with liver cirrhosis.
Among various amino acids, branched-chain amino acids, especially leucine, increased IGF-I production by rat primary cultured hepatocytes. Addition of IGF-I stimulated proliferation, protein production and glucose metabolism by rat hepatocytes. In these cells, mTOR dependent signaling pathway was up-regulated. The stimulatory effect of IGF-I was abrogated by the addition of an inhibitor of mTOR pathway. These observations suggest that IGF-I stimulates hepatocyte function directly, and stimulation of IGF-I production is a possible therapeutic candidate in patients with liver cirrhosis.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (23 results)

All 2010 2009 2008 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (8 results) Remarks (2 results)

  • [Journal Article] Expression of alpha-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.2010

    • Author(s)
      Ohtomo N, Tomiya T, Tanoue Y, Inoue Y, Nishikawa T, Ikeda H, Seyama Y, Kokudo N, Shibahara J, Fukayama M, Koike K, Shirataki H, Fujiwara K
    • Journal Title

      Int J Oncol 37

      Pages: 1417-23

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sex difference in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.2010

    • Author(s)
      Tomiya T
    • Journal Title

      Hepatol Res 40

      Pages: 108-110

    • NAID

      10027407074

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma level of bioactive lipid mediator sphingosine 1-phosphate is reduced in patients with chronic hepatitis C.2010

    • Author(s)
      Ikeda H, Ohkawa R, Watanabe N, Nakamura K, Kume Y, Nakagawa H, Yoshida H, Okubo S, Yokota H, Tomiya T, Nishikawa T, Ohtomo N, Tanoue Y, Koike K, Yatomi Y
    • Journal Title

      Clin Chim Acta 411

      Pages: 765-770

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased production of ADAMTS13 in hepatic stellate cells contributes to enhanced plasma ADAMTS13 activity in rat models of cholestasis and steatohepatitis.2010

    • Author(s)
      Watanabe N, Ikeda H, Kume Y, Satoh Y, Kaneko M, Takai D, Tejima K, Nagamine M, Mashima H, Tomiya T, Noiri E, Omata M, Matsumoto M, Fujimura Y, Yatomi Y
    • Journal Title

      Thromb Haemost 102

      Pages: 389-396

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2.2010

    • Author(s)
      Ikeda H, Watanabe N, Ishii I, Shimosawa T, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Iitsuka S, Fujita R, Omata M, Chun J, Yatomi Y
    • Journal Title

      J Lipid Res 50

      Pages: 556-64

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired liver regeneration in acute liver failure : the significance of cross-communication of growth associated factors in liver regeneration.2010

    • Author(s)
      Tomiya T, Omata M, Imamura H, Fujiwara K
    • Journal Title

      Hepatol Res 38

    • NAID

      10025323134

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sex difference in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.2010

    • Author(s)
      Tomiya T.
    • Journal Title

      Hepatol Res

      Volume: 40 Pages: 108-110

    • NAID

      10027407074

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of alpha-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.2010

    • Author(s)
      Ohtomo N, Tomiya T, et al
    • Journal Title

      Int J Oncol

      Volume: 37 Pages: 1417-1423

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] plasma level of bioactive lipid mediator sphingosine 1-phosphate is reduced in patients with chronic hepatitis C.2010

    • Author(s)
      Ikeda H, Ohkawa R, Watanabe N, Nakamura K, Kume Y, Nakagawa H, Yoshida H, Okubo S, Yokota H, Tomiya T, et al.
    • Journal Title

      Clin Chim Acta

      Volume: 416 Pages: 765-770

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2.2009

    • Author(s)
      Ikeda H, Watanabe N, Ishii I, Shimosawa T, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, et al.
    • Journal Title

      J Lipid Res 50

      Pages: 556-64

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased production of ADAMTS13 in hepatic stellate cells contributes to enhanced plasma ADAMTS13 activity in rat models of cholestasis and steatohepatitis.2009

    • Author(s)
      Watanabe N, Ikeda H, Kume Y, Satoh Y, Kaneko M, Takai D, Tejima K, Nagamine M, Mashima H, Tomiya T, et al.
    • Journal Title

      Thrombo Haemost 102

      Pages: 389-396

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired liver regeneration in acute liver failure: the significance of cross-communication of growth associated factors in liver regeneration.2008

    • Author(s)
      Tomiya T, Omata M, Imamura H, Fuiiwara K
    • Journal Title

      Hepatol Res 38

      Pages: 29-33

    • NAID

      10025323134

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injuryvia sphingosine 1-phosphate receptor 2.2008

    • Author(s)
      Ikeda H, Watanabe. N, Ishii I, Shimosawa T, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, et al.
    • Journal Title

      J Lipid Res 50

      Pages: 556-64

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Insulin-like growth factor I stimulates proliferation and protein production in rat hepatocytes through an mTOR signaling pathway.2010

    • Author(s)
      Tanoue Y, Tomiya T, et al.
    • Organizer
      Annual meeting of the American association for the study of liver diseases
    • Place of Presentation
      Boston, MA U.S.A
    • Year and Date
      2010-10-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Insulin-like growth factor I stimulates proliferation and protein production in rat hepatocytes through an mTOR signaling pathway.2010

    • Author(s)
      Tanoue Y, Tomiya T, Ohtomo N, Nishikawa T, Inoue Y, Shirataki H, Ikeda H, Koike K, Fujiwara K
    • Organizer
      Annual Meeting of the American Association for the Study of the Liver Diseases
    • Place of Presentation
      Boston, Massachusetts
    • Related Report
      2010 Final Research Report
  • [Presentation] Direct effect of insulin-like growth factor I on proliferation and protein production by rat hepatocytes.2010

    • Author(s)
      Tanoue Y, Tomiya T, Ohtomo N, Inoue Y, Nishikawa T, Ikeda H, Shirataki H, Koike K, Fujiwara K
    • Organizer
      FASEB Summer Research Conference : Liver Growth, Injury and Metabolism, Basic and Applied Biology
    • Place of Presentation
      Snowmass, Colorado, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Expression of alpha-taxilin may reflect malignant potential of hepatocellular carcinoma.2009

    • Author(s)
      Ohtomo N, Tomiya T, Tanoue Y, Inoue Y, Nishikawa T, et al.
    • Organizer
      The 60^<th> annual meeting of the American association for the study of liver diseases
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2009-11-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Expression of alpha-taxilin may reflect malignant potential of hepatocellular carcinoma.2009

    • Author(s)
      Ohtomo N, Tomiya T, Tanoue Y, Inoue Y, Nishikawa T, Watanabe N, Ikeda H, Koike K, Seyama Y, Kokudo N, Shibahara J, Shirataki H, Fujiwara K
    • Organizer
      60 th Annual Meeting of the American Association for the Study of the Liver Diseases
    • Place of Presentation
      Boston, Massachusetts
    • Related Report
      2010 Final Research Report
  • [Presentation] Alpha-taxilin, a postulated vesicle traffic protein, may be involved in hepatocyte proliferation.2009

    • Author(s)
      Ohtomo N, Tomiya T, Tanoue Y, Inoue Y, Nishikawa T, Watanabe N, Ikeda H, Omata M, Seyama Y, Kokudo N, Shibahara J, Fukayama M, Shirataki H, Fujiwara K
    • Organizer
      44 th Annual Meeting of the European Association for the Study of the Liver
    • Place of Presentation
      Copenhagen, Denmark
    • Related Report
      2010 Final Research Report
  • [Presentation] Alpha-taxilin,a novel syntaxin-binding protein, is involved in cell proliferation in rat liver2008

    • Author(s)
      Ohtomo N, ToMiya T, Tanoue Y,. Inoue Y, Nishikawa T, Watanabe N, Ikeda H. et al.
    • Organizer
      Faseb Summer Research Conference
    • Place of Presentation
      Snowmass, Colorado, USA
    • Year and Date
      2008-08-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] Alpha-taxillin, a novel syntaxin-binding protein, is involved in cell proliferation in rat liver.2008

    • Author(s)
      Ohtomo N, Tomiya T, Tanoue Y, Inoue Y, Nishikawa T, Watanabe N, Ikeda H, Omata M, Shirataki H, Fujiwara K
    • Organizer
      FASEB Summer Research Conference : Liver Biology, Development and Disease
    • Place of Presentation
      Snowmass, Colorado, USA
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://gastro.m.u-tokyo.ac.jp/med/0201.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://gastro.m.u-tokyo.ac.jp/med/0201.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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