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Clarification of genetic and pathogenic mechanism of syndrome of severe insulin resistance

Research Project

Project/Area Number 18K15660
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Takasawa Kei  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50749463)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインスリン受容体異常症 / インスリン抵抗性 / SGA / 脂肪萎縮症 / DNA損傷修復異常 / 網羅的遺伝子解析 / インスリン受容体 / iPS細胞 / 先天性重症インスリン抵抗性症候群
Outline of Final Research Achievements

Genetic analysis was performed on 18 pediatric patients with type A insulin resistance clinically diagnosed by pediatric endocrinologists, and 12 INSR mutations located in the tyrosine kinase domain of INSR were identified.
Compared with previous reports in Japan and overseas, our study revealed that the extent of growth retardation during the fetal period is correlated with the severity of insulin signaling impairment, suggesting that SGA (small for gestational age) birth may be a clinical feature of insulin resistance type A.

Academic Significance and Societal Importance of the Research Achievements

本研究を通じて、本邦の小児期発症A型インスリン抵抗症の臨床像が明らかになった。また、臨床的に重症インスリン抵抗性症候群と診断される症例の中には、次世代シークエンスによる既存の網羅的遺伝子解析を用いても遺伝学的な原因が同定されない症例が含まれることが確認された。
今後はインスリン受容体異常症および類縁疾患に加え、高度インスリン抵抗性を呈し、若年発症糖尿病をきたす疾患単位として、DNA損傷修復異常を生じるRecQヘリカーゼタンパク異常であるBloom症候群に着目し、DNA損傷修復に関与する分子とインスリン受容体下流カスケードの関連を明らかにする研究を進める。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2021 2020 2019 2018 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Marked clinical heterogeneity in congenital hyperinsulinism due to a novel homozygous ABCC8 mutation2021

    • Author(s)
      Takasawa Kei、Miyakawa Yuichi、Saito Yoko、Adachi Eriko、Shidei Tsunanori、Sutani Akito、Gau Maki、Nakagawa Ryuichi、Taki Atsuko、Kashimada Kenichi、Morio Tomohiro
    • Journal Title

      Clinical Endocrinology

      Volume: - Issue: 6 Pages: 940-948

    • DOI

      10.1111/cen.14443

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prematurity at less than 24 weeks of gestation is a risk for prolonged hyperglycemia in extremely low-birth weight infants2020

    • Author(s)
      Yamauchi Takeru、Imamura Masatoshi、Takasawa Kei、Nakajima Keisuke、Nakagawa Ryuichi、Gau Maki、Sugie Manabu、Taki Atsuko、Kawai Masahiko、Kashimada Kenichi、Morio Tomohiro
    • Journal Title

      Endocrine

      Volume: 70 Issue: 1 Pages: 71-77

    • DOI

      10.1007/s12020-020-02393-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical characteristics of adolescent cases with Type A insulin resistance syndrome caused by heterozygous mutations in the β-subunit of the insulin receptor (INSR) gene2018

    • Author(s)
      Takasawa Kei、Tsuji-Hosokawa Atsumi、Takishima Shigeru、Wada Yasunori、Nagasaki Keisuke、Dateki Sumito、Numakura Chikahiko、Hijikata Atsushi、Shirai Tsuyoshi、Kashimada Kenichi、Morio Tomohiro
    • Journal Title

      Journal of Diabetes

      Volume: 11 Issue: 1 Pages: 46-54

    • DOI

      10.1111/1753-0407.12797

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Bloom症候群はIGF-1不応による成長障害とインスリン抵抗性糖尿病を発症する2020

    • Author(s)
      高澤啓, 宮川雄一, 小野真, 森尾友宏, 鹿島田健一
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 1)Bloom症候群はIGF1不応による成長障害とインスリン抵抗性糖尿病を発症する2019

    • Author(s)
      高澤啓 我有茉希 山内建 中川竜一 宮川雄一 小野真 森尾友宏 鹿島田健一
    • Organizer
      第53会日本小児内分泌学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小児A 型インスリン抵抗症の臨床像と遺伝子型相関2018

    • Author(s)
      高澤 啓、細川 敦美、滝島 茂、和田 泰格、長崎 啓祐、伊達木 澄人、沼倉 周彦、土方 敦司、白井剛、森尾 友宏、鹿島田 健一
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児A型インスリン抵抗症の臨床像と遺伝学的背景2018

    • Author(s)
      高澤 啓、細川 敦美、滝島 茂、和田 泰格、長崎 啓祐、伊達木 澄人、沼倉 周彦、土方 敦司、白井剛、森尾 友宏、鹿島田 健一
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Remarks] 先天性内分泌疾患の分子病態の解明

    • URL

      http://www.tmd.ac.jp/med/ped/medical/research/life_theme.html#04

    • Related Report
      2019 Research-status Report

URL: 

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

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