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Elucidation the roles of senescence-like phenotype in pancreatic beta-cells in diabetic mutant cryptochrome1 transgenic mice

Research Project

Project/Area Number 15K08417
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionYamagata University

Principal Investigator

Okano Satoshi  山形大学, 医学部, 助教 (60300860)

Co-Investigator(Kenkyū-buntansha) 中島 修  山形大学, 医学部, 教授 (80312841)
安井 明  東北大学, 加齢医学研究所, 加齢研フェロー (60191110)
Co-Investigator(Renkei-kenkyūsha) SATOH KENNICHI  東北医科薬科大学, 医学部, 教授 (10282055)
HAYASAKA KIYOSHI  山形大学, 医学部, 名誉教授 (20142961)
Research Collaborator KANNO SHINICHIROU  東北大学, 加齢医学研究所, 講師
IGARASHI MASAHIKO  山形市立病院済生館, 地域糖尿病センター, センター長
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords糖尿病 / 細胞老化関連分泌形質(SASP) / 膵島構造リモデリング / 膵上皮内腫瘍性病変(PanIN) / 膵癌前駆病変 / KPNA2(インポーティンα1) / 膵β細胞-膵管細胞分化転換 / 亜鉛結合変異mCRY1(C414A-CRY1) / 体内時計 / 膵島 / CRY1亜鉛結合モチーフ配列 / 膵上皮内腫瘍性病変 (PanIN) / 膵管細胞 / 繊維化 / 膵癌 / 膵上皮内腫瘍性病変(PanIN) / tubular complex / 膵β細胞新生 / 膵管上皮細胞 / 生物時計 / クリプトクロム(CRY) / HES1 / 膵β細胞 / 脱分化 / 分化転換 / 組織リモデリング / 視交叉上核 / 摂食同調振動体
Outline of Final Research Achievements

Our research group (the study network of Cryptochrome in Tohoku Area [principal investigator: Sstoshi Okano]) have showed that, from the research over 10 years, the zinc-binding site-mutant (C414A) mCRY1 Tg mice display diabetes characterized by β-cell dysfunction due to senescence-like features of pancreatic β-cells.
To elucidate the pathogenesis, we conducted analyses of the pancreas of the aged Tg mice. We newly found that the extent of fibrosis of the islet was higher in Tg mice compared with wild-type controls. Unusual duct-like structures producing mucin developed inside islets in the Tg mice with age. Outside islets, PanIN-like ductal structures, which are surrounded by pancreatic duct glands (PDG), were prominently emerged in aged Tg mice. Our results strongly suggest that, SASP-like microenvironment in the islets of the Tg mice play stimulatory roles in the transdifferentiation of pancreatic β-cells to ductal cells and in the development of ductal dysplasia in the Tg mice.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (11 results) (of which Int'l Joint Research: 7 results)

  • [Journal Article] 亜鉛結合部位変異クリプトクロムタンパク質がマウスにもたらす概日リズムの異常と膵β細胞の障害及び膵管異型病変の生成2018

    • Author(s)
      岡野聡
    • Journal Title

      Bio Clinica (肥満症update)

      Volume: 33(5) Pages: 51-60

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Unique Aspects of Cryptochrome in Chronobiology and Metabolism, Pancreatic β-Cell Dysfunction, and Regeneration: Research into Cysteine414-Alanine Mutant CRY12016

    • Author(s)
      Satoshi Okano
    • Journal Title

      Journal of Diabetes Research

      Volume: 2016 Pages: 3459246-3459246

    • DOI

      10.1155/2016/3459246

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 変異型クリプトクロムタンパク質がマウスにもたらす概日リズムの異常と膵β細胞の障害と新生2016

    • Author(s)
      岡野聡
    • Journal Title

      Bio Clinica 2016年11月号

      Volume: 31(12) Pages: 90-99

    • Related Report
      2016 Research-status Report
    • Acknowledgement Compliant
  • [Journal Article] Unique food-entrained circadian rhythm in Cysteine414-Alanine mutant mCRY1 transgenic mice2016

    • Author(s)
      Okano S, Yasui A, Hayasaka K, Nakajima O
    • Journal Title

      Sleep and Biological Rhythms

      Volume: 印刷中 Issue: 3 Pages: 261-269

    • DOI

      10.1007/s41105-016-0050-1

    • NAID

      40020888020

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 変異型クリプトクロムタンパク質がマウスにもたらす概日リズムの異常と膵β細胞の障害2016

    • Author(s)
      岡野聡
    • Journal Title

      BIO Clinica 2016年6月号 「インクレチン‐最近の話題」

      Volume: 印刷中

    • Related Report
      2015 Research-status Report
    • Acknowledgement Compliant
  • [Presentation] Pancreatic intraepithelial neoplasia-like cells in diabetic cysteine414-alanine-mCRY1 transgenic mice2017

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 佐藤賢一, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      Tohoku Forum on Aging Science (IDAC, Tohoku University)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reduced expression of KPNA2 and dysfunction of β-cells in C414A-CRY1 transgenic mice2017

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      77th Scientific Sessions American Diabetes Association
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Features of pancreatic intraepithelial neoplasia and tubular complex in diabetic cysteine414-alanine-mCRY1 transgenic mice2017

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 佐藤賢一, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      XV European Biological Rhythms Society Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mCRY1-C414A変異体過剰発現マウスの膵臓におけるtubular complexからの膵β細胞の新生とKPNA2の発現2017

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 佐藤賢一, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] C414A変異mCRY1トランスジェニックマウスの膵島の異常と導管構造2016

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Anomalous islet structure in diabetic cysteine414-alanine-mCRY1 transgenic mice2016

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター (宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Anomalous ductal structure in the islet of diabetic cysteine414-alanine-mCRY1 transgenic mice2016

    • Author(s)
      岡野聡, 安井明, 菅野新一郎, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      76th Scientific Sessions American Diabetes Association (ADA)
    • Place of Presentation
      Ernest N. Morial Convention Center (ルイジアナ州ニューオーリンズ)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] システイン414-アラニン変異型CRY1過剰発現マウス膵島の導管様細胞2016

    • Author(s)
      岡野聡, 安井明, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      国立京都国際会館 (京都府京都市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Unusual ductal structure in the islet of diabetic cysteine414-alanine mutant mCRY1 transgenic mice2015

    • Author(s)
      岡野聡, 安井明, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      キーストンシンポジア (糖尿病: 新しい分子メカニズムと治療戦略)
    • Place of Presentation
      ウエスティン都ホテル京都 (京都府京都市)
    • Year and Date
      2015-10-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Food-entrainable circadian rhythm and pathophisiology in Cys414-Ala mCRY1 transgenic mice2015

    • Author(s)
      岡野聡, 安井明, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      第15回ヨーロッパ時間生物学会(EBRS)・第4回世界時間生物学会連合大会(WCC)
    • Place of Presentation
      マンチェスター大学 (イギリス)
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Senescence-like phenotype in pancreatic β-cells in diabetic mutant cryptochrome1 transgenic mice2015

    • Author(s)
      岡野聡, 安井明, 早坂清, 五十嵐雅彦, 中島修
    • Organizer
      第75回米国糖尿病学会(ADA)
    • Place of Presentation
      Boston Convention and Exhibition Center (アメリカ)
    • Year and Date
      2015-06-04
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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