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Development of slowly progressive type 1 diabetes animal models using the CD28 knock-out NOD mouse

Research Project

Project/Area Number 24591319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionOkinaka Memorial Institute for Medical Research (2014)
University of Yamanashi (2012-2013)

Principal Investigator

KOBAYASHI Tetsuro  公益財団法人冲中記念成人病研究所, その他部局等, 研究員 (30113442)

Co-Investigator(Kenkyū-buntansha) AIDA Kaoru  山梨大学, 総合研究部, 准教授 (50184015)
ICHIJO Masashi  山梨大学, 総合研究部, 助教 (50436854)
TAKIZAWA Souichi  山梨大学, 総合研究部, 助教 (80456467)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords糖尿病 / 緩徐1型糖尿病 / NODマウス / CD28 / 緩徐進行1型糖尿病 / 1型糖尿病 / Type 1 diabetes / Innate immunity / ER stress
Outline of Final Research Achievements

The characteristic pathological features of autopsied pancreas of SPIDDM were CD8+ T cell and CD68+ macropthages to the atrophied exocrine pancreas. Sixty percent of SPIDDM pancreas had pancreatic ductal hyperplasia/metaplasia with obstructive pancreatitis (p<0.01 vs. non-diabetic controls). To establish an animal model of SPIDDM, the effect of poly I:C multiple intraperitoneal injection (poly I:C model) or intra-pancreatic ductal injection of Zein-oleic acid-linoleic acids (ZOAL) (ZOAL model) to CD28 knock-out NOD mice was examined. ZOAL model showed marked pancreatic exocrine inflammation composed of CD8+ and CD68+ cells and high occurrence of diabetes, while poly I:C model showed slight exocrine pancreatic inflammation without enhanced occurrence of diabetes.
Conclusion: We could established ZOAL NOD mice model, which resembles with human SPIDDM.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Invited: 1 results)

  • [Journal Article] Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of regenerating gene (REG) protein in fulminant type 1 diabetes.2014

    • Author(s)
      Aida K, Saitoh S, Nishida Y, Yokota S, Ohno S, Mao X, Akiyama D, Tanaka S, Awata T, Shimada A, Oikawa Y, Shimura H, Furuya F, Takizawa S, Ichijo M, Ichijo S, Itakura J, Fujii H, Hashiguchi A, Takasawa S, Endo T, Kobayashi T
    • Journal Title

      PLOS ONE

      Volume: 9(4)

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Antibody-validated proteins in inflamed islets of fulminant type 1 diabetes profiled by laser-capture microdissection followed by mass spectrometry.2014

    • Author(s)
      Nishida Y, Aida K, Kihara M, Kobayashi T
    • Journal Title

      PLOS ONE

      Volume: 9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes2013

    • Author(s)
      Shoichiro TANAKA、Kaoru AIDA、Yoriko NISHIDA, Tetsuro KOBAYASHI
    • Journal Title

      Endocrine Journal

      Volume: 60(7) Pages: 837-845

    • NAID

      10031195751

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ligand-Bound Thyroid Hormone Receptor Contributes to Reprogramming of Pancreatic Acinar Cells Into Insulin-Producing Cells.2013

    • Author(s)
      Furuya F, et. al.,
    • Journal Title

      J Biol Chem.

      Volume: Equb ahead of print

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunization of mice with a newly identified thyroid-stimulating hormone receptor splice variant induces Graves'-like disease.2013

    • Author(s)
      Endo T, et. al.,
    • Journal Title

      J Autoimmun

      Volume: Equb ahead of print

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] High Frequency of HLA B62 in Fulminant Type 1 Diabetes with the Drug-Induced Hypersensitivity Syndrome2013

    • Author(s)
      Hiroshi Onuma, et. al.,
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 97

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 緩徐進行1型糖尿病の膵病変2015

    • Author(s)
      小林哲郎、会田薫、西田頼子、島田朗、八木橋操六、粟田卓也
    • Organizer
      第58回日本糖尿病学会年次学術集会シンポジウム
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21 – 2015-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 1型糖尿病の成因 最先端研究はどこまで解明されたか緩徐進行1型糖尿病の成因と診断基準2014

    • Author(s)
      小林哲郎、田中昌一郎、会田薫
    • Organizer
      第57回日本糖尿病学会年次学術集会シンポジウム
    • Place of Presentation
      リーガロイヤルホテル(大阪)
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 劇症1型糖尿病の膵島内に存在するReg-1αを強発現する腺房細胞様細胞2014

    • Author(s)
      会田薫、斉藤成、西田頼子、横田貞記、大野伸一、茅暁陽、秋山大一郎、高沢伸、小林哲郎
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪国際会場(大阪)
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 劇症1型糖尿病膵島のプロテオミクス解析2013

    • Author(s)
      西田 頼子、會田 薫、田中昌一郎、小林哲郎
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 「緩徐進行1型糖尿病の成因」熊本市、5月16-18日2013

    • Author(s)
      小林哲郎、会田薫、西田頼子、田中昌一郎
    • Organizer
      第56回日本糖尿病学会総会シンポジウム
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 1型糖尿病の成因(緩徐進行1型糖尿病と劇症1型糖尿病)2012

    • Author(s)
      會田薫、他
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵β細胞におけるIFNγ発現についての検討2012

    • Author(s)
      一條昌志、他
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Research-status Report
  • [Presentation] 筋組織へのアミラーゼ遺伝子導入に伴う膵組織所見や膵内分泌能への影響に関する検討2012

    • Author(s)
      田中昌一郎、他
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Research-status Report
  • [Presentation] 2型糖尿病に合併した乾癬に対しDPP-4阻害薬が著効した一症例2012

    • Author(s)
      一條沙耶花、他
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2012 Research-status Report
  • [Presentation] Ligand bound-thyroid hormone receptorcontributes to reprogramming of pancreatic exocrine cells to insulin-producing cells via induction of Ngn3 and MafA2012

    • Author(s)
      Fumihiko Furuya, et. al.,
    • Organizer
      15th International Congress of Endocrinology
    • Place of Presentation
      Frtezza da Basso (Italy)
    • Related Report
      2012 Research-status Report
  • [Presentation] Association of cardio-ankle vascular index with diabetes mellitus related peripheral arterial desease in chronic hemodialysis patients.2012

    • Author(s)
      Fumihiko Furuya, et. al.,
    • Organizer
      15th International Congress of Endocrinology
    • Place of Presentation
      Frtezza da Basso (Italy)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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