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The significance and the mechanisms of virus-induced diabetes susceptibility genes

Research Project

Project/Area Number 18H02853
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionSaga University

Principal Investigator

Nagafuchi Seiho  佐賀大学, 医学部, 特任教授 (00150441)

Co-Investigator(Kenkyū-buntansha) 高橋 宏和  佐賀大学, 医学部, 特任教授 (20607783)
安西 慶三  佐賀大学, 医学部, 教授 (60258556)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords糖尿病 / ウイルス / 感受性遺伝子 / Tyrosine kinase 2 (Tyk2) / Stat / 膵島炎 / インスリン / Tyrosine kinase 2 / stat / 膵島細胞 / 脳心筋炎ウイルス / 膵島 / チロシンキナーゼ2 / Stat2 / インターフェロン / エンテロウイルス受容体 / コクサッキーBウイルス / エンテロウイルス / 1型糖尿病 / 2型糖尿病 / 発症制御機構
Outline of Final Research Achievements

We found second virus-induced diabetes susceptibility gene as Stat2 in virus-induced diabetes susceptible strain DBA/2 mouse. The expression level of the gene was significantly reduced restrictive in pancreatic beta-cells. The virus infected islets did not have inflammatory cell infiltrations at the time of extensive damage of beta cells at 3 days after infection.
We also found patients with type 2 diabetes, possessing polymorphisms of human virus-induced diabetes susceptibility gene: TYK2 promoter variant, present non-obese, reduced insulin resistant condition along with reduced insulin secretion activity. Review article regarding virus-induced susceptibility genes was published in microorganism in 2020.

Academic Significance and Societal Importance of the Research Achievements

本研究は、マウスおよびヒトに共通するウイルス糖尿病感受性遺伝子を世界に先駆けて同定し、国際的なウイルス糖尿病研究にブレークスルーをもたらした極めて画期的かつ独創的な研究成果である。
さらに、近い将来、ヒトのウイルス糖尿病発症機序を優れて模倣するウイルス糖尿病高感受性ヒト化マウスを作出することにより、糖尿病原因ウイルスを高感度に特定することが可能となる。その結果、科学的証拠に立脚したウイルス糖尿病予防ワクチン開発が、医学のみならず社会的にも加速され、ウイルス糖尿病の予防につながり、1型、2型いずれの糖尿病患者においても、その発症率の低下につながることが期待できる。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report

Research Products

(12 results)

All 2021 2020 2019 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] TYK2 Promoter Variant Is Associated with Impaired Insulin Secretion and Lower Insulin Resistance in Japanese Type 2 Diabetes Patients.2021

    • Author(s)
      Mori H, Takahashi H, Mine K, Higashimoto K, Inoue K, Kojima M, Kuroki S, Eguchi T, Ono Y, Inuzuka S, Soejima H, Nagafuchi S, Anzai K.
    • Journal Title

      Genes

      Volume: 12 Pages: 400-400

    • DOI

      10.3390/genes12030400

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired upregulation of Stat2 gene restrictive to pancreatic β-cells is responsible for virus-induced diabetes in DBA/2 mice.2020

    • Author(s)
      Mine, K.; Nagafuchi, S.; Hatano, S.; Tanaka, K.; Mori, H.; Takahashi, H.; Anzai, K.; Yoshikai, Y.
    • Journal Title

      Biochem Biophys Res Commun 521:853-860

      Volume: 521 Pages: 853-860

    • DOI

      10.1016/j.bbrc.2019.10.193

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic Susceptibility of the Host in Virus-Induced Diabetes.2020

    • Author(s)
      Mine K, Yoshikai Y, Takahashi H, Mori H, Anzai K, Nagafuchi S.
    • Journal Title

      Microorganisms

      Volume: 8 Pages: 1133-1133

    • DOI

      10.3390/microorganisms8081133

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Viruses with masked pathogenicity and genetically susceptible hosts―How to discover potentially pathogenic viruses.2019

    • Author(s)
      Nagafuchi, S.; Mine, K.; Takahashi, H.; Anzai, K.; Yoshikai, Y.
    • Journal Title

      J. Med. Virol.

      Volume: 91 Pages: 1365-1467

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ウイルス感染と糖尿病2019

    • Author(s)
      三根敬一朗、永淵正法、吉開泰信
    • Journal Title

      日本臨牀

      Volume: 別冊 内分泌症候群(第3版) Pages: 84-88

    • Related Report
      2019 Annual Research Report
  • [Presentation] EMC-Dウイルス誘発糖尿病におけるメスの感受性に関する検討2020

    • Author(s)
      三根敬一朗、森仁恵、高橋宏和、吉開泰信、安西慶三、永淵正法
    • Organizer
      第63回日本糖尿病学会年次学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] NOD マウスにおけるTyk2 遺伝子の意義の解明2020

    • Author(s)
      三根敬一朗、吉開泰信、森仁恵、高橋宏和、安西慶三、永淵正法
    • Organizer
      第58回日本糖尿病学会九州地方会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Pancreatic beta cell specific reduced Stat2 gene expression isresponsible for serving susceptibility to virus-induced diabetes in DBA/2 mice2019

    • Author(s)
      Mine K, Nagafuchi S, Mori, H, Takahashi K, Yoshikai Y, Anzai K.
    • Organizer
      55th ANNUAL MEETING EASD
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Promoter Variant of TYK2,a Putative Virus-Induced Susceptibility Gene,Is Associated with Impaired Insulin Secretion and Nonobese Type2 Diabetes.2019

    • Author(s)
      Mori H, Takahashi H, Mine M, Inoue K, Kojima M, Kuroki S, Ono Y, Inuzuka S, Nagafuchi S, Anzai K.
    • Organizer
      Food Security Heart & Diabetes
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ウイルス感染時にけるDBA/2マウス膵β細胞の解析2019

    • Author(s)
      三根敬一朗、皆川洋子、永淵正法
    • Organizer
      第60回日本臨床ウイルス学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規ウイルス糖尿病感受性遺伝子の同定と発症メカニズムの解析2019

    • Author(s)
      三根敬一朗、森仁恵、高橋宏和、吉開泰信、安西慶三、永淵正法
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Remarks] ウイルス糖尿病予防ワクチン開発への挑戦

    • URL

      http://diabetic-virus-action.net/

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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