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

• Project/Area Number: 20590761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The 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: ¥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.

Research Products

• [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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Alpha-taxilin,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. et al.
  • Organizer: Faseb Summer Research Conference
  • Place of Presentation: Snowmass, Colorado, USA
  • Year and Date: 2008-08-05
• [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
• [Remarks] ホームページ等
  • URL: http://gastro.m.u-tokyo.ac.jp/med/0201.html
• [Remarks]
  • URL: http://gastro.m.u-tokyo.ac.jp/med/0201.html