• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular Mechanism of beta cell failure due to autophagic failure

Research Project

Project/Area Number 20H03735
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionJuntendo University

Principal Investigator

Hirotaka Watada  順天堂大学, 大学院医学研究科, 教授 (60343480)

Co-Investigator(Kenkyū-buntansha) 西田 友哉  順天堂大学, 医学部, 准教授 (10581449)
宮塚 健  順天堂大学, 大学院医学研究科, 客員教授 (60622363)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2020: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords膵β細胞 / オートファジー / 2型糖尿病
Outline of Research at the Start

我々はこれまで、2型糖尿病におけるオートファジー不全の病態解明を行ってきた。その過程でオートファジー不全による膵β細胞不全に対する代償機構の鍵因子である可能性のあるAutophagy failure induced gene (AFIG)1の同定と、細胞内オートファジーフラックス調節候補因子Autophagy flux regulator (AFR)1の同定に至った。本申請においては膵β細胞恒常性維持におけるAFIG1とオートファジーにおけるAFR1の機能解明を通じて2型糖尿病における膵島オートファジー不全の病態及び遺伝因子との関連を解明し新規治療標的の同定を目指す。

Outline of Final Research Achievements

We have reported that autophagy failure is an important determinant of islet dysfunction and have elucidated the pathogenesis of autophagy failure in type 2 diabetes. In the process, we have identified an autophagy failure―induced gene (AFIG)1 that may be involved in the compensatory mechanism for pancreatic β-cell failure due to autophagy failure and a candidate factor for intracellular autophagy flux regulator (AFR)1 (AFR)1, a candidate regulator of intracellular autophagy flux. In this application, we have elucidated the functions of AFIG1 in pancreatic β-cell homeostasis and AFR1 in autophagy, but could not confirm the importance of these factors.

Academic Significance and Societal Importance of the Research Achievements

我々の研究グループは、膵β細胞におけるオートファジー機能不全が膵β細胞機能不全に関与することを世界に先駆けて解明したものの、その詳細な分子機構の解明に関してはなかなか進んでいなかった。そこでトランスクリプトーム解析やCRISPR/Cas9システムを用いたスクリーニング系により、その鍵因子候補を同定し、今回、機能解析を行った。残念ながら、これらの因子の重要性を示せなかったが、膵β細胞機能不全の分子メカニズムの同定は糖尿病の膵β細胞不全の病態解明とともに、オートファジー調節機構の新たな知見の解明を通じて細胞生物学分野の進歩にも大きく貢献することが期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (3 results)

All 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Monitoring autophagic flux in vivo revealed its physiological response and significance of heterogeneity in pancreatic beta cells2023

    • Author(s)
      Aoyama Shuhei、Nishida Yuya、Uzawa Hirotsugu、Himuro Miwa、Kanai Akiko、Ueki Kyosei、Ito Minami、Iida Hitoshi、Tanida Isei、Miyatsuka Takeshi、Fujitani Yoshio、Matsumoto Masaki、Watada Hirotaka
    • Journal Title

      Cell Chemical Biology

      Volume: - Issue: 6 Pages: 658-671.e4

    • DOI

      10.1016/j.chembiol.2023.03.001

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic β-cell function under autophagy deficiency2022

    • Author(s)
      Fukae Toshinaru、Miyatsuka Takeshi、Himuro Miwa、Wakabayashi Yuka、Iida Hitoshi、Aoyama Shuhei、Mita Tomoya、Ikeda Fuki、Haruna Hidenori、Takubo Noriyuki、Nishida Yuya、Shimizu Toshiaki、Watada Hirotaka
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 612 Pages: 99-104

    • DOI

      10.1016/j.bbrc.2022.04.092

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cumulative autophagy insufficiency in mice leads to progression of β-cell failure2022

    • Author(s)
      Suzuki L, Miyatsuka T, Himuro M, Wakabayashi Y, Osonoi S, Miura M, Katahira T, Fujitani Y, Iida H, Mizukami H, Nishida Y, Watada H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 611 Pages: 38-45

    • DOI

      10.1016/j.bbrc.2022.04.040

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi