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Research of prevention of type 1 diabetes by thiazolidine derivative.

Research Project

Project/Area Number 17590931
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKobe University

Principal Investigator

NAGATA Masao  Kobe University, Graduate School of Medicine, Associate Professor (70294220)

Co-Investigator(Kenkyū-buntansha) YOKONO Koichi  Kobe University, Graduate School of Medicine, Professor (50144580)
MORIYAMA Hiroaki  Kobe University, Graduate School of Medicine, COE Research Fellow (70372646)
NAKAMURA Masato  Kyoto Prefectual University of Medicine, 大学院・医学系研究科, Associate Professor (40227921)
TAKAHASHI Kazuma  Iwate Medical University, 医学部, Lecturer (60292215)
KAWAMURA Tomoyuki  Osaka City University, Graduate School of Medicine, Assistant Professor (60271186)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,680,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsType 1 diabetes / Thiazolidine derivative / Pioglitazone / Dendritic cells / NOD mouse / ピオグリタゾン / 緩徐進行型1型糖尿病 / NKT細胞 / チアゾリン誘導体 / 液体食事負荷試験
Research Abstract

1. Prevention of type 1 diabetes by pioglitazone in NOD mice
Oral administration of pioglitazone prevented overt diabetes in female NOD mice not only from 4 weeks of age but also from 10 weeks of age when most of pancreas already showed intra-islet cellar infiltration. Transfer experiments using spleen cells to NOD-scid mice revealed that effector activity was decreased, whereas immuno-regulatory activity was not enhanced by pioglitazone administration_ Flow cytometric analysis showed that CD25^+ CD4^+ T cells were not increased but NKT cells were increased by pioglitazone. Cell surface of dendritic cells showed the increased expression of CD80, co-stimulatory molecule B7-1, and CD1d. These results suggested that the characteristics of dendritic cells were changed by pioglitazone and enhanced NKT cells, leading the autoimmune response to pancreatic β cells. Our study revealed that modification of dendritic cells is one of powerful strategy to prevent type 1 diabetes.
2. Prevention of the progression of pancreatic β cell destruction in human type 1 diabetes
To evaluate the effect of pioglitazone on human type 1 diabetes, we administered pioglitazone with intensive insulin therapy to acute type 1 diabetes. During 2 years follow up, three patients with pioglitazone 30mg/day showed progressive decrease of serum C-peptide level and required much more dose of insulin to control blood sugar. Furthermore, one slowly progressive patient became keto-acidosis after 23 months administration of pioglitazone. These results suggests that at least ordinal dose of pioglitazone cannot inhibit progression of β cell destruction in human type 1 diabetes.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (30 results)

All 2008 2007 2006 2005 Other

All Journal Article (24 results) (of which Peer Reviewed: 8 results) Presentation (5 results) Book (1 results)

  • [Journal Article] Immunological aspects of 'fulminant type 1 diabetes'2008

    • Author(s)
      Nagata M, et. al.
    • Journal Title

      Diabetes Res Clin Pract.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prevention of recurrent but not spontaneous autoimmuno diabetes by transplanted NOD islets adenovirally transduced with immunomodulating molecules.2008

    • Author(s)
      Sakata M, et. al.
    • Journal Title

      Diabetes Res Clin Pract. 80(3)

      Pages: 352-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Low-dose warfarin functions as an immunomodulator to prevent cyclo phosphamide-induced NOD diabetes.2008

    • Author(s)
      Kurohara M, et. al.
    • Journal Title

      Kobe J. Med. Sci. (印刷中)(In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prevention of recurrent but not spontaneous autoimmune diabetes by transplanted NOD islets adenovirally transduced with immunomodulating molecules2008

    • Author(s)
      Sakata, M, Yasuda, H, Moriyama, H, Yamada, K, Kotani, R, Kurohara, M, Okumachi, Y, Kishi, M, Arai, T, Hara, K, Hamada, H, Yokono, K, Nagata, M
    • Journal Title

      Diabetes Res Clin Pract 80(3)

      Pages: 352-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prevention of recurrent but not spontaneous autoimmune diabetes by transplanted NOD islets adenovirally transduced with immunomodulating molecules.2008

    • Author(s)
      Sakata M
    • Journal Title

      Diabetes Res Clin Pract. (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose warfarin functions as an immunomodulator to prevent cyclophosphamid e-induced NOD diabetes.2008

    • Author(s)
      Kurohara M
    • Journal Title

      Kobe J. Med. Sci. (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modification of the Rb-binding Domain of Replication-Competent Adenovirus Vector Enhances Cytotoxicity Against Human Esophageal Cancers via NF-kB Activity2007

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

      Hum Gene Ther. 18(5)

      Pages: 389-400

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knockout NOD mice.2007

    • Author(s)
      Moriyama H, et. al.
    • Journal Title

      Diabetes Res Clin Pract.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Immunological aspects of `fulminant type 1 diabetes'2007

    • Author(s)
      Nagata, M, H. Moriyama, R. Kotani, H. Yasuda, M. Kishi, M. Kurohara, K. Hara, K. Yokono
    • Journal Title

      Diabetes Res Clin Pract S99-S103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Modification of the Rb-binding Domain of Replication-Competent Adenovirus Vector Enhances Cytotoxicity Against Human Esophageal Cancers via NF-kB Activity2007

    • Author(s)
      Yamada, K, Moriyama, H, Yasuda, H, Hara, K, Maniwa, Y, Hamada, H, Koichi, Yokono, Nagata, M
    • Journal Title

      Hum Gene Ther 18(5)

      Pages: 389-400

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knockout NOD mice2007

    • Author(s)
      Moriyama, H., Nagata, M., T., Arai, Y., Okumachi, K., Yamada, R., Kotani, H., Yasuda, K., Hata, K, Yokono
    • Journal Title

      Diabetes Res Clin Pract S155-160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Immunological aspects of fulminant type 1 diabetes.2007

    • Author(s)
      Nagata M
    • Journal Title

      Diabetes Res Clin Pract. 77S

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knockout NOD mice.2007

    • Author(s)
      Moriyama H
    • Journal Title

      Diabetes Res Clin Pract. 77S

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Modification of the Rb-binding domain of replication-competent adenoviral vector enhances cytotoxicity against human esophageal cancers via NF-kappaB activity.2007

    • Author(s)
      Yamada K
    • Journal Title

      Hum Gene Ther. 18

      Pages: 389-400

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the insulin knouckout NOD mice.2007

    • Author(s)
      Moriyama H
    • Journal Title

      Diabetes Research & Clinical Practice (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immunological Aspects of 'Fulminant Type 1 Diabetes'2007

    • Author(s)
      Nagata M
    • Journal Title

      Diabetes Research & Clinical Practice (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulation of hypoxia-inducible factor 1 by glucose availability under hypoxic conditions2007

    • Author(s)
      Zhou J
    • Journal Title

      Kobe medical Journal (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Modification of the Rb-binding Domain of Replication-Competent Adenovirus Vector Enhances Cytotoxicity Against Human Esophageal Cancers via NF-κB Activity2007

    • Author(s)
      Yamada K
    • Journal Title

      Human Gene Therapy (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] T cell epitope mapping study with insulin overlapping peptides using ELISPOT assay in Japanese children and adolescents with type 1 diabetes.2006

    • Author(s)
      Higashide T
    • Journal Title

      Pediatr。 Res。 59 (3)

      Pages: 445-450

    • Related Report
      2006 Annual Research Report
  • [Journal Article] T cell epitope mapping study with insulin overlapping peptides using ELISPOT assay in Japanese children and adolescents with type 1 diabetes.2006

    • Author(s)
      Higashide Takashi
    • Journal Title

      Pediatr Res. 59(3)

      Pages: 445-450

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prevention of the manifestation of diabetes in the elderly in the presymptomatic stage2006

    • Author(s)
      永田 正男
    • Journal Title

      Nippon Ronen Igakkai Zasshi. 43

      Pages: 84-86

    • NAID

      10020554609

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A possible association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma2 gene with obesity in native Javanese in Indonesia.2005

    • Author(s)
      Danawati C Wahyu
    • Journal Title

      Diabetes Metab Res Rev. 21(5)

      Pages: 465-469

    • Related Report
      2005 Annual Research Report
  • [Journal Article] E1B-deleted adenovirus replicates in p53-deficient lung cancer cells due to the absence of apoptosis.2005

    • Author(s)
      Harada N
    • Journal Title

      Oncol Rep. 14(5)

      Pages: 1155-1163

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Low-dose warfarin functions as an immunomodulator to prevent cyclophosphamide-induced NOD diabetes

    • Author(s)
      Kurohara, M, Yasuda, H, Moriyama, H, Sakata, M, Yamada, K, Kotani, R, Nakayama, M, Hara, K, Yokono, K, Nagata, M
    • Journal Title

      Kobe J. Med. Sci (in press)

    • NAID

      110006648210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Preventive effect of NOD^<LPR/LPR_>derived dendritic cells to autoimmune diabetes via fas-fasL interaction.2007

    • Author(s)
      Kishi M.
    • Organizer
      9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium
    • Place of Presentation
      Miami USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intravenous administration of murine proinsulin1 or 2 expressing recombinant adenovirus vector protects diabetes in NOD mice.2007

    • Author(s)
      K Yamada
    • Organizer
      9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium
    • Place of Presentation
      Miami USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Preventive effect of NODLPR/LPR_derived dendritic cells to autoimmune diabetes via fas-fasL interaction.2007

    • Author(s)
      Kishi M
    • Organizer
      9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium
    • Place of Presentation
      Miami, USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Pioglitazone投与によるNODマウスの糖尿病発症制御2006

    • Author(s)
      黒原みどり
    • Organizer
      第49回日本糖尿病学会年次学術集会・総会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] TGF-β1-Modelated Dendritic Cells Inducing High CDld Expression Result in Prevention of Autoimmune Diabetes In NOD Mice2006

    • Author(s)
      Yasuda H.
    • Organizer
      66th Scientific Sessions of American Diabetes Association
    • Place of Presentation
      Washington, DC USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Public Health Policy and Approaches for Noncommunicable Disease Prevention and Control in Japan : A case study2005

    • Author(s)
      Masao Nagata
    • Total Pages
      55
    • Publisher
      World Health Organization, Centre for Health development, Kobe, Japan
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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