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Elucidation of pancreatic beta cell differentiation and maturation mechanism by monoamines

Research Project

Project/Area Number 26461036
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Institute of Technology

Principal Investigator

Sakano Daisuke  東京工業大学, 生命理工学院, 助教 (40571039)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsインスリン / β細胞 / 分化 / 脱分化 / モノアミン / ドーパミン / 膵臓 / 膵β細胞 / 自己複製 / 分泌 / 低分子化合物 / 複製 / KOマウス / VMAT2
Outline of Final Research Achievements

We screened compounds that promote cell proliferation of mouse pancreatic β cells using 3,000 low molecular weight compounds. As a result, Domperidon (DPD) which is an antagonist of dopamine D2 receptor (Drd2) was identified. And it was also revealed that DPD has a strong dedifferentiation suppressing effect and cell death suppressing effect in addition to an increase of self-replicating ability of β cell.
Furthermore, the formation of a heterodimer between Drd 2 and the adenosine A 2a receptoris important to control cell differentiation, dedifferentiation, cell division and cell death (Sakano et al., Stem Cell R eports, 2015).

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2016 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (4 results) Remarks (3 results)

  • [Journal Article] Dopamine D2 receptor-mediated regulation of pancreatic b cell mass.2016

    • Author(s)
      1.Sakano D, Choi S, Kataoka M, Shiraki N, Uesugi M, Kume K, Kume S
    • Journal Title

      Stem Cell Reports

      Volume: 7 Issue: 1 Pages: 95-109

    • DOI

      10.1016/j.stemcr.2016.05.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pancreatic differentiation from murine embryonic stem cells. Methods Mol Biol.2016

    • Author(s)
      Sakano D, Shiraki N, Kuem S
    • Journal Title

      Methods Mol Biol.

      Volume: 1341 Pages: 417-423

    • DOI

      10.1007/7651_2015_217

    • ISBN
      9781493929535, 9781493929542
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Beneficial effect of insulin treatment on islet transplantation outcomes in akita mice.2014

    • Author(s)
      Kikawa K, Sakano D, Shiraki N, Tsuyama T, Kume K, Endo F, Kume S.
    • Journal Title

      Plos one

      Volume: 9(4) Issue: 4 Pages: e95451-e95451

    • DOI

      10.1371/journal.pone.0095451

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Generation of insulin-producing beta-like cells from human iPS cells in a defined and completely Xeno-free culture system.2014

    • Author(s)
      Shahjalal HM, Shiraki N, Sakano D, Kikawa H, Ogaki S, Baba H, Kume K., Kume S.
    • Journal Title

      Journal of Molecular Cell Biology

      Volume: 6 Issue: 5 Pages: 394-408

    • DOI

      10.1093/jmcb/mju029

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] VMAT2 identified as a regulator of late-stage beta cell differentiation.2013

    • Author(s)
      Sakano, D., Shiraki, N., Kikawa, K., Yamazoe, T., Kataoka, M., Umeda, K., Araki, K., Mao, D., Matsumoto, S., Nakagata, N., Andersson, O., Stainier, D., Endo, F., Kume, K., Uesugi, M. and Kume, S.
    • Journal Title

      Nat. Chem. Biol.

      Volume: 10 Issue: 2 Pages: 141-148

    • DOI

      10.1038/nchembio.1410

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Monoamine signals that control differentiation and proliferation of pancreatic beta cells2016

    • Author(s)
      粂 昭苑
    • Organizer
      CDBシンポジウム2016
    • Place of Presentation
      理化学研究所 多細胞システム形成研究センター(CDB)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] モノアミンシグナルによる膵β細胞の増殖・分化の制御2016

    • Author(s)
      坂野大介、崔 成翼、片岡正光、白木伸明、粂昭苑
    • Organizer
      日本生化学会
    • Place of Presentation
      宮城県
    • Related Report
      2016 Annual Research Report
  • [Presentation] モノアミンシグナルによる膵β細胞の分化・増殖制御、2016

    • Author(s)
      坂野大介、崔 成翼、片岡正光、白木伸明、粂昭苑
    • Organizer
      厚生労働省「ヒト幹細胞情報化推進事業」SKIP Seminar
    • Place of Presentation
      東京都
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] モノアミンを介したシグナル伝達による膵島の構造・機能の制御2015

    • Author(s)
      坂野大介
    • Organizer
      第3回細胞凝集研究会
    • Place of Presentation
      鹿児島
    • Year and Date
      2015-11-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Monoamine signals that control differentiation and proliferation of pancreatic beta cells.2015

    • Author(s)
      粂 昭苑
    • Organizer
      2016 Keystone Symposia Conference T2: Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
    • Place of Presentation
      京都
    • Year and Date
      2015-10-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膵β細胞の複製を促進する低分子化合物の探索2014

    • Author(s)
      坂野 大介、崔 成翼、片岡 正光、粂 昭苑
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Book] 「膵β細胞研究の進化と展望」 『多能性幹細胞から膵β細胞への分化を制御するシグナル』Islet Equality2014

    • Author(s)
      坂野大介、粂昭苑
    • Total Pages
      4
    • Publisher
      メディカルレビュー社
    • Related Report
      2014 Research-status Report
  • [Book] 「膵β細胞・膵島の再生研究」『特集 糖尿病-診断・治療update-』2014

    • Author(s)
      坂野大介、粂昭苑
    • Total Pages
      6
    • Publisher
      最新医学社
    • Related Report
      2014 Research-status Report
  • [Book] 「糖尿病と代謝」『iPS細胞を用いた膵β細胞研究の最前線』、Diabetes Journal2014

    • Author(s)
      坂野大介、粂昭苑
    • Total Pages
      6
    • Publisher
      協和企画
    • Related Report
      2014 Research-status Report
  • [Book] 「膵島バイオロジーの新たな展開」『幹細胞を用いた膵β細胞誘導研究』、Diabetes Frontier2014

    • Author(s)
      坂野大介、粂昭苑
    • Total Pages
      6
    • Publisher
      協和企画
    • Related Report
      2014 Research-status Report
  • [Remarks] ドーパミンD2受容体を介して 膵臓のβ細胞量が調節される

    • URL

      http://educ.titech.ac.jp/bio/news/2016_07/052422.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 多能性幹細胞分野 坂野大介助教、粂昭苑教授ら、マウスES細胞から膵臓細胞を作製することに成功しました

    • URL

      http://kumanichi.com/news/local/main/20131216002.shtml

    • Related Report
      2014 Research-status Report
  • [Remarks] 小胞型モノアミン輸送体VMAT2は膵臓β細胞の分化を制御する

    • URL

      http://first.lifesciencedb.jp/archives/8151

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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