Development of strategies for improvement of insulin resistance of the aged by targeting the blood coagulation system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K20663
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Studies on the Super-Aging Society
• Research Institution: Kagawa University
• Principal Investigator: Hirano Katsuya 香川大学, 医学部, 教授 (80291516)
• Co-Investigator(Kenkyū-buntansha): 橋本 剛 香川大学, 医学部, 助教 (80380153)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: 血液凝固因子 / 受容体 / プロテイナーゼ活性化型受容体 / インスリン抵抗性 / 老化

Outline of Final Research Achievements

In the mice that lack the gene encoding PAR1, a receptor for blood coagulation factors, we found that the aging-associated obesity, insulin resistance and fatty liver were prevented. When the PAR1-deficient mice were fed high fat diet, the obesity and insulin resistance developed just as in the case of normal mice that express the PAR1 gene. Our findings suggest that some aging-associated events were specifically suppressed in the PAR1-deficient mice. PAR1 is therefore anticipated to be a useful target for developing anti-aging strategies.

Free Research Field

生理学、健康科学、老年医学、代謝内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究は、PAR1遺伝子欠損マウスにおいて、肝臓、骨格筋、脂肪組織に共通してインスリン分解酵素の発現が高いことを見出した。加齢に伴い凝固活性が亢進すると、PAR1を介してインスリン分解酵素の発現が低下し、慢性的にインスリン濃度が高い状況が続くことで、インスリン抵抗性が発症する機序が示唆された。本研究成果は、未だ謎が多い高齢者の糖尿病に特異的な仕組みの解明につながる点で学術的意義が高く、高齢者の糖尿病に特異的な予防治療法の開発につながる点で社会的意義が高い。