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2004 Fiscal Year Final Research Report Summary

Stem cell regulation for the differenntiiation of insulin-produucing cells

Research Project

Project/Area Number 14207046
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

TANIGUCHI Hideki  Yokohama City University Graduate School of Medicine, Department of Regenerative Medicine, Prof., 大学院・医学研究科, 教授 (70292555)

Co-Investigator(Kenkyū-buntansha) NAKAUCHI Hiromitsu  The University Tokyo, The Institute of Medical Science, Prof., 医科学研究所, 教授 (40175485)
Project Period (FY) 2002 – 2004
KeywordsPancreas / Regeneration / Stem Cell / Diabetes
Research Abstract

By combining flow cytometry and clonal analysis, we show that a candidate pancreatic stem cell and progenitor population that reside in the developing mouse pancreas expresses the receptor for the hepatocyte growth factor c-Met, but do not express hematopoietic and vascular endothelial antigens such as CD45, TER119, c-Kit, and Flk-1, which formed clonal colonies in vitroand differentiated into multiple pancreatic lineage cells. Some of them could expand with self-renewal cell divisions in culture, and following cell transplantation, they differentiated into pancreatic islet and acinar cells in vivo. By using this antigen, pancreatic stem cells can be isolated prospectively, enabling a detailed investigation of stem cell markers, and application towards regenerative therapies for diabetes mellitus.
Glucagon-like peptide (GLP)-1 is produced through posttranslational processing of proglucagon and acts as a regulator of various homeostatic events. Among its analogs, however, the function of GLP-1-(1-37), synthesized in small amounts in the pancreas, has been unclear. We find that GLP-1-(1-37) induces insulin production in developing and, to a lesser extent, adult intestinal epithelial cells in vitro and in vivo, a process mediated by upregulation of the Notch-related gene ngn3 and its downstream targets, which are involved in pancreatic endocrine differentiation. These cells became responsive to glucose challenge in vitro and reverse insulin-dependent diabetes after implantation into diabetic mice. Our findings suggest that efficient induction of insulin production in intestinal epithelial cells by GLP-1-(1-37) could represent a new therapeutic approach to diabetes mellitus.

  • Research Products

    (22 results)

All 2004 2003 2002

All Journal Article (10 results) Book (12 results)

  • [Journal Article] Prospective Isolation of Multipotent Pancreatic Progenitors Using Flow-Cytometric Cell Sorting2004

    • Author(s)
      Suzuki A
    • Journal Title

      Diabetes 53(8)

      Pages: 2143-2152

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prospective Isolation of Multipotent Pancreatic Progenitors Using Flow-Cytometric Cell Sorting2004

    • Author(s)
      Suzuki, A.
    • Journal Title

      Diabetes 53(8)

      Pages: 2143-2152

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Deversity of Hepatic Stem Cells in the Fetal and Adult Liver.2003

    • Author(s)
      Zheng Y.W
    • Journal Title

      Seminars in Liver Disease 23(4)

      Pages: 337-348

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vitro production of functionally mature hepatocytes from prospectively isolated hepatic stem2003

    • Author(s)
      Suzuki A
    • Journal Title

      Cell Transplantation 12

      Pages: 469-473

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Glucagon-like peptide-1 (1-37) converts intestinal epithelial cells into insulin-producing cells2003

    • Author(s)
      Suzuki A
    • Journal Title

      Proc Nat Acad Sci USA 100(9)

      Pages: 5034-5039

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells2003

    • Author(s)
      Suzuki A
    • Journal Title

      Development 130

      Pages: 2513-2524

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Diversity of Hepatic Stem Cells in the Fetal and Adult Liver2003

    • Author(s)
      Zheng, Y. W.
    • Journal Title

      Seminars in Liver Disease 23(4)

      Pages: 337-348

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] In vitro production of functionally mature hepatocytes from prospectively isolated hepatic stem2003

    • Author(s)
      Suzuki, A.
    • Journal Title

      Cell Transplantation 12

      Pages: 469-473

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Glucagon-like peptide-1 (1-37) converts intestinal epithelial cells into insulin-producing cells2003

    • Author(s)
      Suzuki, A.
    • Journal Title

      Proc Nat Acad Sci USA 100(9)

      Pages: 5034-5039

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells2003

    • Author(s)
      Suzuki, A.
    • Journal Title

      Development 130

      Pages: 2513-2524

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 上皮-間葉間の可塑性(Epithelial-Mesenchymal Transition : EMT)-遺伝子医学MOOK再生医療へのブレイクスルー-2004

    • Author(s)
      菅野雅人
    • Total Pages
      5
    • Publisher
      メディカル ドゥ
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝幹細胞を用いた再生治療の基盤科学 ヒト疾患モデル-難病の病態解明と診断・治療への応用-2004

    • Author(s)
      谷口英樹
    • Total Pages
      8
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝臓の再生-幹細胞を利用した微小組織エレメントの再構成-再生医療工学2004

    • Author(s)
      谷口英樹
    • Total Pages
      1
    • Publisher
      工業調査会
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] GLP-1(1-37)によるインスリン産生細胞の分化誘導 分子糖尿病学の進歩2004

    • Author(s)
      谷口英樹
    • Total Pages
      9
    • Publisher
      金原出版
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝臓における幹細胞生物学.肝・胆・膵疾患の最新医療2003

    • Author(s)
      谷口英樹
    • Total Pages
      4
    • Publisher
      先端医療技術研究所
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝臓の再生-幹細胞を利用した再生治療-再生医療-ティッシュエンジニアリング&生体材2003

    • Author(s)
      谷口英樹
    • Total Pages
      7
    • Publisher
      日刊工業出版プロダンクション
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 微小重力環境の利用.再生医療-ティッシュエンジニアリング&生体材料最前線2003

    • Author(s)
      谷口英樹
    • Total Pages
      2
    • Publisher
      日刊工業出版プロダクション
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 「臓器置換」から「臓器再生」へ-再生医療のイノベーション-2003

    • Author(s)
      谷口英樹
    • Total Pages
      55
    • Publisher
      エルゼア・ジヤパン
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝幹細胞の分離と臨床応用へのアプローチ.再生医学2003

    • Author(s)
      谷口英樹
    • Total Pages
      7
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝臓における再生療法の将来展望.現代医療の最前線2003

    • Author(s)
      谷口英樹
    • Total Pages
      13
    • Publisher
      最新医学社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 造血幹細胞から肝細胞への分化.造血幹細胞-基礎から遺伝子治療・再生医療へ2002

    • Author(s)
      谷口英樹
    • Total Pages
      4
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 肝臓幹細胞.再生医療工学の最先端(筏義人編集)2002

    • Author(s)
      谷口英樹
    • Total Pages
      7
    • Publisher
      シーエムシー出版
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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