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Elucidation of insulin secretory mechanisms through large scale generation of genetically-modified insulin secreting cells and omics analysis

Research Project

Project/Area Number 17K09850
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionNihon University

Principal Investigator

ISHIHARA Hisamitsu  日本大学, 医学部, 教授 (60361086)

Co-Investigator(Kenkyū-buntansha) 藤城 緑  日本大学, 医学部, 助教 (50420211)
渡邉 健太郎  日本大学, 医学部, 准教授 (80373017)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膵島 / インスリン / メタボローム / トランスクリプトーム / インスリン分泌 / 解糖系 / TCAサイクル / オミックス / 膵β細胞 / 遺伝子改変
Outline of Final Research Achievements

In this project, we have studied mechanisms of impaired insulin secretion underlying diabetes pathogenesis. We have modulated expression of glucose-metabolizing enzymes in insulin secreting cells. In addition, since we have found that Tspan molecular family members are modulated in poorly responding insulin secreting cells, we studied Tspan proteins. We identified glucose-metabolizing enzymes and a member of the Tspan family plays important roles in insulin secretion.

Academic Significance and Societal Importance of the Research Achievements

本研究において、インスリン分泌β細胞において、ブドウ糖の代謝に障害を与えるとミトコンドリアでの代謝が低下し、インスリン分泌が低下するが、インスリン含有量はむしろ増加する可能性が示唆された。これらは、糖尿病初期に認められる現象と類似しており、そのメカニズムをさらに解析して介入できるようにすることは、糖尿病の発症予防に役立つ方策を考案する上で重要であると考えられた。一方、インスリン分泌の低下した細胞で変動したテトラスパニン分子の一部は、インスリン分泌障害の結果ではなく、原因になっている可能性が考えられ、今後の治療ターゲットとして有望であると考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice2019

    • Author(s)
      Inoue Masa-Ki、Matsunaga Yasuka、Nakatsu Yusuke、Yamamotoya Takeshi、Ueda Koji、Kushiyama Akifumi、Sakoda Hideyuki、Fujishiro Midori、Ono Hiraku、Iwashita Misaki、Sano Tomomi、Nishimura Fusanori、Morii Kenichi、Sasaki Kensuke、Masaki Takao、Asano Tomoichiro
    • Journal Title

      Diabetology & Metabolic Syndrome

      Volume: 11 Issue: 1 Pages: 57-57

    • DOI

      10.1186/s13098-019-0454-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two adult siblings with myotonic dystrophy type 1 with different phenotypes presenting with chronic respiratory insufficiency and sleep apnea syndrome2019

    • Author(s)
      3.Kohno G, Ogawa K, Kushimoto M, Tanaka S, Ikeda J, Nishizawa T, Mitsuke K, Nakayama T, Suzuki Y, Ishihara H, Fujishiro M.
    • Journal Title

      Front Neurol

      Volume: 10 Pages: 681-681

    • DOI

      10.3389/fneur.2019.00681

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16.2019

    • Author(s)
      Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue MK, Mizuno Y, Nakanishi M, Sano T, Yamawaki Y, Kushiyama A, Sakoda H, Fujishiro M, Ryo A, Ono H, Minamino T, Takahashi SI, Ohno H, Yoneda M, Takahashi K, Ishihara H, Katagiri H, Nishimura F, Kanematsu T, Yamada T, Asano T.
    • Journal Title

      Cell Rep.

      Volume: 26 Issue: 12 Pages: 3221-3230

    • DOI

      10.1016/j.celrep.2019.02.066

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Trk-fused gene (TFG) regulates pancreatic β cell mass and insulin secretory activity.2017

    • Author(s)
      Yamamotoya T, Nakatsu Y, Kushiyama A, Matsunaga Y, Ueda K, Inoue Y, Inoue MK, Sakoda H, Fujishiro M, Ono H, Kiyonari H, Ishihara H, Asano T.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-017-13432-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion2017

    • Author(s)
      Nakatsu Y, Mori K, Matsunaga Y, Yamamotoya T, Ueda K, Inoue Y, Mitsuzaki-Miyoshi K, Sakoda H, Fujishiro M, Yamaguchi S, Kushiyama A, Ono H, Ishihara H, Asano T.
    • Journal Title

      J Biol Chem.

      Volume: 292 Issue: 28 Pages: 11886-11895

    • DOI

      10.1074/jbc.m117.780726

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Roles of glycolysis distinct from mitochondrial metabolism for signal generation in insulin secreting cells2020

    • Author(s)
      Ishihara H, Nishioka H, Yamana M, Nagasawa A, Koike M, Saito H, Morikawa A, Kosuda M
    • Organizer
      The 80th Scientific Sessions of American Diabetes Assosication
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ビルビン酸輸送担体欠損インスリン分泌細胞株の樹立と解析2020

    • Author(s)
      西岡 秀典、山名 碧、長澤 瑛子、小須田南、石原寿光
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Overexpression screening identifies mitochondrial carbonic anhydrase 5b as an important regulator of glucose-stimulated insulin secretion in beta-cells2019

    • Author(s)
      Kosuda M, Yamaguchi S, Nakasawa A, Yamana M, Koike M, NIshioka H, Ishihara H.
    • Organizer
      American Diabetes Association 79th Scientific Sessions
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] MIN6細胞における解糖系中間体によるインスリン産生制御2019

    • Author(s)
      山名碧、藤城緑、藤城緑、山口賢、江頭富士子、藤城緑、渡邉健太郎、石原寿光
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 膵β細胞におけるChrono遺伝子の機能解析2019

    • Author(s)
      山口賢、長澤瑛子、山名碧、小須田南、石原寿光
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 異なる耐糖能障害の形成を呈した筋緊張性ジストロフィー1型の兄妹例2019

    • Author(s)
      河野玄太、藤城緑、久志本優、池田迅、田中翔、岡本真由美、江頭富士子、小川克彦、鈴木裕、中山智祥、石原寿光
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ブドウ糖応答性の異なるMIN6細胞サブクローンのトランスクリプトーム解析によるインスリン分泌に重要な遺伝子の探索2018

    • Author(s)
      田中彩、古川麻美、小須田南、山名碧、山口賢、石原寿光
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] インスリン分泌におけるCITED4の機能解析2018

    • Author(s)
      山口賢、田中彩、小須田南、山名碧、長澤瑛子、石原寿光
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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