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

2019 Fiscal Year Final Research Report

• Project/Area Number: 17KK0198
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Jichi Medical University
• Principal Investigator: Ushijima Kentaro 自治医科大学, 医学部, 講師 (70448843)
• Project Period (FY): 2018 – 2019
• Keywords: 体内時計 / 糖尿病 / 臓器連関

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.

Free Research Field

時間生物学

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。