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Regeneration Therapy Diabetes Using the Pancreatic Stem Cell System

Research Project

Project/Area Number 13470222
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionInstitute for Molecular and Cellular Regulation, Gunma University

Principal Investigator

KOJIMA Itaru  Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (60143492)

Co-Investigator(Kenkyū-buntansha) 張 有青  群馬大学, 生体調節研究所, 助手 (10302499)
最上 秀夫  浜松医科大学, 医学部, 助教授 (90311604)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2002: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2001: ¥9,700,000 (Direct Cost: ¥9,700,000)
Keywordsregeneration medicine / insulin / pancreatic stem cell / differentiation / diabetes mellitus / activin / betacellulin / 膵β細胞 / 幹細胞
Research Abstract

The final goal of our study is to establish a new therapeutic approach for treatment of type II diabetes. In the present study, we investigate to elucidate the characteristics of the pancreatic stem cells and regulatory mechanism for the regulation of growth and differentiation of these cells. We first studied the changes in the expression of transcription factors during the differentiation of AR42J, a model of the pancreatic stem cells, during differentiation to insulin-producing cells. We found that activin A induced differentiation to endocrine cells and neurogeninB is a critical transcription factor. We then studied the changes in the expression of activin A in the pancreatic duct after reduction of the beta cell mas. We found that the expression of activin A was induced after the reduction of the beta cell mass. Given that activin A is a critical differentiation factor for the pancreatic stem cells, the induction of acivin A in the pancreatic duct may be a crucial step for the initiation of the beta cell neogenesis. Finally, we extablished a culture of the pancreatic ductal cells and found that these cells differentiate into insulin-secreting cells after the treatment with a combanation of activn A and betacellulin. We are currently studying the properties of differentiated cells.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Zhang, Y.Q., Mashima, H., Kojima, I.: "Changes in the expression of transcription factors in AR42J cells during differentiation to insulin-secreting cells"Diabates. 50. S10-S14 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujimaki, S., Kubohara, Y., Kobayashi, I., Kojima, I.: "Caspase-independent apoptosis induced by DIF in INS-I cells"Eur.J.Pharmacol.. 421. 93-100 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Endocrinology. 142. 5379-5385 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima, I., Nakamura, T., et al.: "Combined expression of PDX-1 and ISI-1 induces immature enterocytes to produce insulin"Diabetes. 51. 1398-1409 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang, Y.Q., Zhang, H., Maeshima, A., Miyagawa, I., Kojima, I.: "Up-regulation of the expression of activins in the pancreatic duct by reduction of the β cell mass"Endocrinology. 143. 3540-3547 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Huang, W.H., Shen, L., Eto, Y., Kojima I., Gaisano, H.: "Effects of selective exocrine or endocrine induction of AR42J on SNARE and Munc18 expresssion"Pancreas. 25. 56-63 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang, Y.Q., Maeshima,H. and Kojima, I.: "Changes in the expression of transcription factors in AR42J cells during differentiation to insulin-secreting cells"Diabetes. 50. S10-S14 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujimaki, S., Kubohara, Y., Kobayashi, I. and Kojima, I.: "Caspase-independent apoptosis induced by DIF in INS-I cells"Eur. J. Pharmacol.. 421. 93-100 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li, L., Seno, M., Yamada, H. and Kojima, I.: "Promotion of cell regeneration by betacellulin in 90% pancreatectomized rats."Endocrinology. 142. 5379-5385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kojima, H., Nakamura, T. et al.: "Combined expression of PDX-1 and lsl-1 induces immature enterocytes to produce insulin"Diabetes. 51. 1398-1409 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang, Y.Q., Zhang, H., Maeshima, A., Kubohara, H. and kojima, I.: "Up-regulation of the expression of activins in the pancreatic duct by reduction of the βcell mass"Endocrinology. 143. 3540-3547 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Huang, W.H., Shen, L, Eto, Y., Kojima. I and Gaisano, H.: "Effects of selective exocrine o rendocrine induction of AR42J on SNARE and Munc18 expression"Pancreas. 25. 56-63 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zhang, Y.Q., Zhang, H., Maeshima, A., Kurihara, H., Miyagawa, J., Kojima, I.: "Up-regulation of the expression of activins in the pancreatic duct by reduction of the β cell mass"Endocrinology. 143. 3540-3547 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Huang, W.H., Sheu, I., Eto, Y., Kojima, I., Gaisano, H.: "Effect of selective endocrine or excrine induction of AR42J on SNARE and Munc18 expression"Pancreas. 25. 56-63 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morita, T., Koyama, H., Yamamura, H.et al.: "Expression and its role of calponin in pancreas AR42J cell differentiation into insulin-producing cells"Diabetes. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mashima, H., Ueda, N., Ohno, H.et al.: "A novel mitochondrial ca^<2+> -dependent solute carrier in the liver identified by mRNA differential display"J. Blol. Chem.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zhang, Y.Q., Mashima, H., Kojima, I.: "Changes in the expression of transcription factors in AR42J cells during differentiation into insulin-secreting cells"Diabetes. 50. S10-S14 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Li, L., Seno, M., Yamada, S., Kojima, I.: "Promotion of β cell regeneration by betacellulin in 90% pancreatectomized rats"Endocrinology. 142. 5379-5385 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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