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Exploring mechanisms of distorted glucagon secretion in type 1 diabetes using a novel alpha-cell model of insulin deficiency

Research Project

Project/Area Number 25461367
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionOsaka Medical College

Principal Investigator

Mishiba Yuko  大阪医科大学, 医学部, 助教 (80377415)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsグルカゴン / 膵α細胞 / 1型糖尿病 / メタボローム解析
Outline of Final Research Achievements

To investigate the metabolic traits that underlie the distortion of glucagon secretion in insulin deficiency, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for type 1 diabetes (T1D), which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response in T1D.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (16 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] 1型糖尿病におけるグルカゴン分泌異常2016

    • Author(s)
      三柴裕子、今川彰久
    • Journal Title

      Diabetes Frontier

      Volume: 27 (2) Pages: 229-233

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes2014

    • Author(s)
      Bessho M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 11 Pages: e113254-e113254

    • DOI

      10.1371/journal.pone.0113254

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus2014

    • Author(s)
      Miyasato M, Murase-Mishiba Y, Bessho M, Miyawaki M, Imbe H, Tsutsumi C, Tanimoto K, Imagawa A, Terasaki J, Hanafusa T.
    • Journal Title

      Clin Chim Acta

      Volume: 433C Pages: 184-189

    • DOI

      10.1016/j.cca.2014.03.018

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycaemic instability correlates with a hyperglucagonaemic response in patients with type 1 diabetes without residual beta-cell function2013

    • Author(s)
      Bessho M, Murase-Mishiba Y, Tsutsumi C, Haseda F, Imagawa A, Terasaki J, Hanafusa T.
    • Journal Title

      Diabetes Res Clin Pract

      Volume: 102 Issue: 2 Pages: e38-e40

    • DOI

      10.1016/j.diabres.2013.09.003

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD4+ CD45RA- FoxP3high activated regulatory T cells are functionally impaired and related to residual insulin-secreting capacity in patients with type 1 diabetes.2013

    • Author(s)
      Haseda F, Imagawa A, Murase-Mishiba Y, Terasaki J, Hanafusa T.
    • Journal Title

      Clin Exp Immunol.

      Volume: 173 Issue: 2 Pages: 207-216

    • DOI

      10.1111/cei.12116

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Characterization of a pancreatic alpha-cell model of insulin-deficient diabetes by metabolome analysis2015

    • Author(s)
      Bessho-Tachibana M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T
    • Organizer
      The International Diabetes Federation 23rd World Diabetes Congress (IDF 2015)
    • Place of Presentation
      バンクーバー (カナダ)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of a pancreatic alpha-cell model of insulin-deficient diabetes by metabolome analysis: a possible pathogenetic role of taurine2015

    • Author(s)
      Bessho-Tachibana M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T
    • Organizer
      Keystone Symposia Conference: Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
    • 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 Annual Research Report
    • Int'l Joint Research
  • [Presentation] インスリン分泌が枯渇した1型糖尿病における食事負荷に対するグルカゴン分泌動態の検討2015

    • Author(s)
      三柴裕子、橘 恵、宮里 舞、堤 千春、弘田弘子、稲葉惟子、佐野寛行、中辻文彦、谷本啓爾、金綱規夫、大西峰樹、今川彰久、寺前純吾、花房俊昭
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] GLP-1(Glucagon-like peptide-1)受容体作動薬 exenatideのマウス自己免疫性関節炎に対する効果2015

    • Author(s)
      佐野寛行、長谷田文孝、堤 千春、谷本啓爾、金綱規夫、三柴裕子、大西峰樹、寺前純吾、花房俊昭
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 劇症1型糖尿病患者急性期血清において高値を認める新規抗体2015

    • Author(s)
      長谷田文孝、今川彰久、西川博嘉、三井しのぶ、藤澤玲子、堤 千春、佐野寛行、三柴裕子、寺前純吾、坂口志文、花房俊昭
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 2型糖尿病患者におけるSGLT2阻害薬の有用性と食行動の関係2015

    • Author(s)
      大西峰樹、寺前純吾、三柴裕子、花房俊昭、2型糖尿病患者におけるSGLT2阻害薬の有用性と食行動の関係
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Possible contribution of taurine to distorted glucagon secretion in insulin deficiency: A metabolome analysis using a novel α-cell model of type 1 diabetes2014

    • Author(s)
      Bessho M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T.
    • Organizer
      第50回欧州糖尿病学会議(EASD)
    • Place of Presentation
      ウイーン(オーストリア)
    • Year and Date
      2014-09-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Characterization of a pancreatic alpha-cell model of type 1 diabetes employing metabolome analysis2014

    • Author(s)
      Murase-Mishiba Y, Terasaki J, Hanafusa T.
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] インスリンレセプターノックダウン膵α細胞におけるグルコース濃度の変化に対するグルカゴン分泌動態の検討2014

    • Author(s)
      別所 恵、三柴 裕子、寺前 純吾、今川 彰久、花房 俊昭.
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      リーガロイヤルホテル(大阪府大阪市)
    • Year and Date
      2014-05-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 1型糖尿病における食事負荷に対するグルカゴン分泌動態の検討 -血糖変動、内因性インスリン分泌との関連-2014

    • Author(s)
      宮里 舞、三柴 裕子、堤 千春、長谷田 文孝、佐野 寛行、別所 恵、宍倉 佳名子、中辻 文彦、忌部 尚、宮脇 正博、大西 峰樹、今川 彰久、寺前 純吾、花房 俊昭.
    • Organizer
      第57回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-05-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 内因性インスリン分泌が完全に枯渇した1型糖尿病患者におけるグルカゴン分泌能と血糖不安定性との関連2013

    • Author(s)
      別所 恵、三柴 裕子、堤 千春、長谷田 文孝、寺前 純吾、今川 彰久、花房 俊昭
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本市国際交流会館
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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