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Mechanisms of regulation of development of pancreatic beta cells by Notch signal for beta cell regeneration therapy

Research Project

Project/Area Number 16590904
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKYOTO UNIVERSIIY

Principal Investigator

HOSODA Kiminori  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 講師 (40271598)

Co-Investigator(Kenkyū-buntansha) ITO Hiroshi  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (40252457)
HAMADA Yoshio  National Institute For Basic Biology, Research Associate, 培養育成研究施設, 助手 (10132739)
MASUZAKI Hiroaki  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00291899)
HAYASHI Tatsuya  Kyoto University, Graduate School of Human and Environmental Studies, Associate Professor, 人間・環境学研究科, 助教授 (00314211)
EBIHARA Ken  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70362514)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsdiabetes / pancreas / notch / RBP-J / beta cells / インスリン / Notch1 / Notch2
Research Abstract

To investigate the precise role of Notch/Rbp-j signaling in the pancreas, we inactivated Rbp-j by crossing Rbp-j foxed mice with Pdx.cre or Rip.cre transgenic mice. The loss of Rbp-j at the initial stage of pancreatic development induced accelerated alpha and PP cell differentiation and a concomitant decrease in the number of Neurogenin3 (Ngn3)-positive cells at E11.5. Then at E15, elongated tubular structures expressing ductal cell markers were evident ; however, differentiation of acinar and all types of endocrine cells were reduced. During later embryonic stages, compensatory acinar cell differentiation was observed. The resultant mice exhibited insulin-deficient diabetes with both endocrine and exocrine pancreatic hypoplasia. In contrast, the loss of Rbp-j specifically in beta cells did not affect beta cell number and function. Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (20 results)

All 2006 2005 2004

All Journal Article (20 results)

  • [Journal Article] Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas.2006

    • Author(s)
      J.Fujikura, K.Hosoda, et al.
    • Journal Title

      Cell Metab. 3・1

      Pages: 59-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Gene Expression of a Membrane-Bound Fatty Acid Receptor, GPR40, in Pancreas and Islet Cell Tumors in Humans-Evidence for GPR40 Expression in Pancreatic Beta Cells and Its Implication in Insulin Secretion in Humans-2006

    • Author(s)
      T.Tomita, K.Hosoda, et al.
    • Journal Title

      Diabetologia. (in press)

      Pages: 2006-2006

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Low-intensity contraction activates the {alpha}1 isoform of 5'AMP-activated protein kinase in rat skeletal muscle.2006

    • Author(s)
      T.Toyoda, K.Hosoda, et al.
    • Journal Title

      Am J Physiol Endocrinol Metab. 90・E

      Pages: 583-590

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas.2006

    • Author(s)
      J.Fujikura, K.Hosoda, et al.
    • Journal Title

      Cell Metab. 3(1)

      Pages: 56-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene Expression of a Membrane-Bound Fatty Acid Receptor, GPR4O, in Pancreas and Islet Cell Tumors in Humans- Evidence for GPR40 Expression in Pancreatic Beta Cells and Its Implication in Insulin Secretion in Humans -2006

    • Author(s)
      T.Tomita, K.Hosoda, et al.
    • Journal Title

      Diabetologia. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Low-intensity contraction activates the {alpha}1 isoform of 5'AMP-activated protein kinase in rat skeletal muscle.2006

    • Author(s)
      T.Toyoda, K.Hosoda, et al.
    • Journal Title

      Am J Physiol Endocrinol Metab. 90(E)

      Pages: 583-590

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene Expression of a Membrane-Bound Fatty Acid Receptor, GPR40, in Pancreas and Islet Cell Tumors in Humans- Evidence for GPR40 Expression in Pancreatic Beta Cells and Its Implication in Insulin Secretion in Humans -2006

    • Author(s)
      T.Tomita, K.Hosoda, et al.
    • Journal Title

      Diabetologia. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice.2005

    • Author(s)
      H.Iwakura, K.Hosoda, et al.
    • Journal Title

      J. Biol. Chem. 280・15

      Pages: 15247-15256

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification.2005

    • Author(s)
      T.Tanaka, K.Hosoda, et al.
    • Journal Title

      Diabetes. 54・8

      Pages: 2365-2374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] GPR40 gene expression in human pancreas and insulinoma.2005

    • Author(s)
      T.Tomita, K.Hosoda, et al.
    • Journal Title

      Biochem Biophys Res Commun. 338・4

      Pages: 1788-1790

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice.2005

    • Author(s)
      H.Iwakura, K.Hosoda, et al.
    • Journal Title

      J.Biol.Chem. 285(15)

      Pages: 15247-15256

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification.2005

    • Author(s)
      T.Tanaka, K.Hosoda, et al.
    • Journal Title

      Diabetes. 54(8)

      Pages: 2365-2374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GPR40 gene expression in human pancreas and insulinoma.2005

    • Author(s)
      T.Tomita, K.Hosoda, et al.
    • Journal Title

      Biochem Biophys Res Commun. 338(4)

      Pages: 1788-1790

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice.2005

    • Author(s)
      H.Iwakura, K.Hosoda, et al.
    • Journal Title

      J.Biol.Chem. 280・15

      Pages: 15247-15256

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of Rat Insulin II Promoter-Ghrelin Transgenic Mice and Rat Glucagon Promoter-Ghrelin Transgenic Mice.2005

    • Author(s)
      H.Iwakura, K.Hosoda et al.
    • Journal Title

      J.Biol.Chem. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CCAAT/enhancer binding protein αmaintains the ability of insulin-stimulated GLUT4 translocation in 3T3-C2 fibroblastic cells.2005

    • Author(s)
      M.Fujimoto, K.Hosoda et al.
    • Journal Title

      Biochimica et Biophysica Acta-Molecular Cell Research. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes.2004

    • Author(s)
      M.Fujimoto, K.Hosoda et al.
    • Journal Title

      FEBS Lett. 576(3)

      Pages: 492-497

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association of Ob-R gene polymorphism and insulin resistance in Japanese men.2004

    • Author(s)
      A.Takahashi-Yasuno, K.Hosoda et al.
    • Journal Title

      Metabolism. 53(5)

      Pages: 650-654

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese : a novel homozygous nonsense mutation in seipin gene.2004

    • Author(s)
      K.Ebihara, K.Hosoda et al.
    • Journal Title

      J.Clin.Endocrinol.Metab. 89

      Pages: 2360-2364

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reduction of diet-induced obesity in mice overexpressing uncoupling protein 3 in skeletal muscle.2004

    • Author(s)
      C.Son, K.Hosoda et al.
    • Journal Title

      Diabetologia. 47

      Pages: 47-54

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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