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Mechanism of peripheral clock abnormalities caused by disturbance of central-peripheral tissue linkage

Research Project

Project/Area Number 17KK0198
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionJichi Medical University

Principal Investigator

Ushijima Kentaro  自治医科大学, 医学部, 講師 (70448843)

Project Period (FY) 2018 – 2019
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywords体内時計 / 糖尿病 / 臓器連関 / 時計遺伝子 / エネルギー代謝 / 概日リズム
Outline of Final Research Achievements

I investigated a mechanism by which the expression of the clock gene is reduced in the adipose tissue of diabetic mice from the aspect of leptin signaling.
Experiments of measuring histone modification levels and mRNA expression level of the target clock genes suggested that the hypothalamic leptin signal only exerts a small effect on the impairment of the peripheral clock function in adipose tissue.
On the other hand, I have clarified that deletion of Bmal1, one of the upstream clock genes, prolonged phosphorylation of target proteins responding to intracellular calcium signal, and that this effect was specific to pancreatic β cells.

Academic Significance and Societal Importance of the Research Achievements

末梢組織における体内時計の異常が、糖尿病などの代謝性疾患を引き起こすことを支持する知見が集積している。本研究の成果は、インスリン分泌によりエネルギー代謝調節に寄与する膵β細胞において、体内時計による臓器特異的な細胞機能調節機構の存在を示唆するものである。本研究は体内時計異常が糖尿病を引き起す機序解明の一端を担うものであり、本研究の成果は、体内時計およびその調節システムを指標とした糖尿病治療薬の創薬シーズを探索する研究へ発展できると期待される。

Report

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

    (3 results)

All 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Peer Reviewed: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Northwestern University(米国)2018

    • Year and Date
      2018-06-01
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Induction of Dbp by a histone deacetylase inhibitor is involved in amelioration of insulin sensitivity via adipocyte differentiation in ob/ob mice.2019

    • Author(s)
      1.Suzuki C, Ushijima K#, Ando H, Kitamura H, Horiguchi M, Akita T, Yamashita C, Fujimura A.
    • Journal Title

      Chronobiology International

      Volume: 印刷中 Issue: 7 Pages: 955-968

    • DOI

      10.1080/07420528.2019.1602841

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Remarks] Researchmap webページ

    • URL

      https://researchmap.jp/ken_ushijima

    • Related Report
      2019 Annual Research Report

URL: 

Published: 2018-01-25   Modified: 2022-06-09  

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