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Pancreatic islet pathological changes, clinical course, and prognostic prediction based on type 2 diabetes susceptibility gene polymorphism

Research Project

Project/Area Number 18K08462
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionHirosaki University

Principal Investigator

Mizukami Hiroki  弘前大学, 医学研究科, 教授 (00374819)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords2型糖尿病 / 膵臓 / 膵島 / β細胞 / 一塩基多型 / 2型糖尿病 / 1塩基多型 / ALDH1A3 / 遺伝 / β細胞減少 / 膵β細胞 / SNPs / 膵島病理
Outline of Final Research Achievements

1. SNPs analysis: 111 autopsy cases (32 type 2 diabetes cases, 79 non-type 2 diabetes cases) from Hirosaki University were selected. Genomic DNA was extracted from liver and kidney tissues collected at autopsy. After confirming the quality of the DNA, the Japonica array (Toshiba) comprehensively examined the SNPs of the DNA.
2. Pathological analysis: Pancreatic islet cell/amyloid volume and cell dynamics are analyzed. Using pancreatic slices, (1) each endocrine cell volume of pancreatic islets, (2) proliferation of islet cells, (3) islet cell death, and (4) pancreatic cell neogenesis were evaluated.
Similar to previous reports, we found decreased β-cell volume, increased α-cell volume, and increased islet neogenesis in type 2 diabetes.

Academic Significance and Societal Importance of the Research Achievements

本研究において剖検組織を用いて膵島の病理学的変化と遺伝学的変化を相関させる試みを行った。病理学的検索により、糖尿病検体では膵β細胞容積の減少、分化転換の増加が認められた。遺伝子学的検索では、東芝のジャポニカアレーで100症例以上の剖検検体のSNPデータを得ることができた。これら病理学的データ、SNPデータは現在解析中であるが、病理学的変化との関連が得ることができれば、本邦における2型糖尿病の新たな病態の解明につながる可能性がある。さらに、遺伝子変化を標的とした新規治療も期待される。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Int'l Joint Research] KAIST(韓国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University Western Ontario(カナダ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Development of monoclonal mouse antibodies that specifically recognize pancreatic polypeptide2019

    • Author(s)
      Hara A, Nakagawa Y, Nakao K, Tamaki M, Ikemoto T, Shimada M, Matsuhisa M, Mizukami H, Maruyama N, Watada H, Fujitani Y.
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 5 Pages: 459-468

    • DOI

      10.1507/endocrj.EJ18-0441

    • NAID

      130007655243

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 臨床医が知っておくべき糖尿病の基礎5 膵内分泌細胞の可塑性と2型糖尿病2021

    • Author(s)
      水上浩哉
    • Organizer
      第55回 糖尿病学の進歩
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] SD10-2 糖尿病の病態解析の進展2021

    • Author(s)
      水上浩哉
    • Organizer
      第110回 日本病理学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Possible Implication of Cyclin D2 in β Cell Proliferation of Human Perinatal Islet2020

    • Author(s)
      Sho Osonoi, Takanori Sasaki, Kazuhiro Kudo, Soroku Yagihashi, Hiroki Mizukami
    • Organizer
      80th american diabetes association scientific sessions
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 急性心筋梗塞合併2型糖尿病は膵島病理学的所見により亜分類される2019

    • Author(s)
      水上浩哉、高橋和久、遅野井祥、郭 丹やん、工藤和洋、板橋智映子、八木橋操六
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 膵島アミロイド沈着と低酸素関連分子の発現について2019

    • Author(s)
      新井仁、遅野井祥、高橋和久、工藤和洋、板橋智映子、八木橋操六、水上浩哉
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 新しい2型糖尿病亜分類の膵島病理学的所見に基づく検証2019

    • Author(s)
      水上浩哉、高橋和久、遅野井 祥、工藤和洋、板橋智映子、八木橋操六
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Islet cell plasticity and its significance in diabetes Plasticity of human beta cells in type 2 diabetes of Japanese subjects2019

    • Author(s)
      Hiroki Mizukami
    • Organizer
      American Diabetes Association The 79th Scientific Sessions
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Augmented b-Cell Loss in Japanese Patients with Type 2 Diabetes Complicated with Acute Myocardial Infarction2018

    • Author(s)
      Hiroki Mizukami, Kazuhisa Takahashi, Tetsuyuki Tateda, Wataru Inaba, Soroku Yagihashi
    • Organizer
      American Diabetes association 78th Scientific Sessions
    • Related Report
      2018 Research-status Report
  • [Presentation] Symposium 2 How far have we learned the role of glucagon? Pathological alteration of alpha and beta cells in human type 2 diabetes2018

    • Author(s)
      Hiroki Mizukami
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 2型糖尿病を病理学的に研究する2018

    • Author(s)
      水上浩哉
    • Organizer
      第80回 病理診断学講座 Seminar in Diagnostic Pathology
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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