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Mechanism of pancreatic beta-cell proliferation regulated by nervous system

Research Project

Project/Area Number 16K09762
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionYokohama City University

Principal Investigator

Ito Yuzuru  横浜市立大学, 医学部, 講師 (00512980)

Co-Investigator(Kenkyū-buntansha) 寺内 康夫  横浜市立大学, 医学研究科, 教授 (40359609)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords膵β細胞 / アセチルコリン / GLP-1 / 副交感神経 / インスリン / 糖尿病
Outline of Final Research Achievements

This study investigated the role of muscarinic agonists or acetylcholine in regulating the pancreatic β-cell mass and glucose homeostasis. The β-cell mass and proliferation increased following oral administration of bethanechol in wild-type mice. The muscarinic agonists also increased the incorporation of BrdU into islets isolated from wild-type mice and MIN6 cells. In IRS-2 knockout mice, oral administration of the muscarinic agonist did not increase the β-cell mass or proliferation. The phosphorylation of Akt induced by oral administration of bethanechol was observed in wild-type mice, but not in IRS-2 knockout mice. The secretion of GLP-1 was also stimulated by bethanechol in wild-type mice, and the GLP-1 antagonist partially inhibited the bethanechol-induced increase in the β-cell mass. This proliferative effect was dependent on the IRS-2/Akt pathway. The bethanechol-stimulated release of GLP-1 may be indirectly associated with β-cell proliferation.

Academic Significance and Societal Importance of the Research Achievements

ムスカリニックレセプターアゴニストの投与によりマウスでの膵β細胞増殖作用や膵島での血糖依存的なインスリン分泌増強作用を認めることから、新規糖尿病治療薬のターゲットになりえると考えた。in vivoでは、マウスへのbethanechol投与による血糖改善、膵β細胞量増加のモデルを確立し、in vitroでは、マウス単離膵島やMIN6細胞におけるbethanechol刺激によるBrdU取り込みモデルを確立した。こうしたモデルの確立により、アセチルコリンによる膵β細胞への直接的、間接的な作用機序の研究推進が望める。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2019 2018 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Indicators of the need for insulin treatment and the effect of treatment for gestational diabetes on pregnancy outcomes in Japan2016

    • Author(s)
      Ito Y, Shibuya M, Hosokawa S, Motoki Y, Nagata R, Konishi H, Miyazaki T, Matsunaga T, Nomura Y, Mihara T, Ito S, Sugiura K, Terauchi Y.
    • Journal Title

      Endocrine Journal

      Volume: 63 Issue: 3 Pages: 231-237

    • DOI

      10.1507/endocrj.EJ15-0427

    • NAID

      130005140779

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 妊娠糖尿病患者における日内血糖変動高値、インスリン治療、分娩後耐糖能異常の各リスク因子の比較検討2019

    • Author(s)
      伊藤譲、澁谷誠、寺内康夫ほか
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 妊娠糖尿病患者の入院血糖日内変動とインスリン治療導入予測因子の検討2018

    • Author(s)
      伊藤譲、澁谷誠、寺内康夫ほか
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 妊娠糖尿病患者の入院血糖日内変動とインスリン治療導入予測因子の2018

    • Author(s)
      伊藤譲、澁谷誠、寺内康夫ほか
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 副交感神経伝達物質による膵β細胞量調節の解析2017

    • Author(s)
      伊藤譲、田島一樹、富樫優、寺内康夫
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Presentation] ムスカリニックアゴニストによる膵β細胞増殖機構の解析2017

    • Author(s)
      伊藤譲、田島一樹、富樫優、寺内康夫
    • Organizer
      第31回日本糖尿病・肥満動物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 副交感神経伝達物質による膵β細胞量調節の解析2016

    • Author(s)
      伊藤譲、折目和基、田島一樹、富樫優、寺内康夫
    • 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

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Published: 2016-04-21   Modified: 2020-03-30  

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