Novel Physiological and Pathophysiological Roles of XOR in Insulin Resistance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K11654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Juntendo University
• Principal Investigator: Satoh HIroaki 順天堂大学, 医学部, 教授 (20323595)
• Co-Investigator(Kenkyū-buntansha): 森谷 千尋 順天堂大学, 医学部, 助教 (90645037)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: XOR / 糖尿病 / インスリン抵抗性

Outline of Final Research Achievements

Many observational studies have reported a positive correlation between hyperuricemia and insulin resistance, but the causal relationship is unknown. In this study, we focused on XOR, an enzyme important in the production of uric acid, and investigated the effect of XOR on insulin resistance using the XOR inhibitor febuxostat; XOR inhibitors significantly increased insulin sensitivity in peripheral tissues but did not significantly alter insulin sensitivity in the liver. We elucidated that XOR inhibitors enhance insulin sensitivity by directly inhibiting XOR in skeletal muscle.
These results suggest that XOR is not only involved in uric acid production but may also be closely related to the pathogenesis of insulin resistance in skeletal muscle.

Free Research Field

代謝・内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究では、XORは尿酸産生に関与するばかりでなく、骨格筋でのインスリン抵抗性の病態にも深く関与していることを明らかにした。 本研究の成果により、骨格筋におけるXORとインスリン抵抗性との関連が解明され、インスリン抵抗性の新たな発症機序の解明につながると期待される。さらに今後ますます重要と考えられるインスリン抵抗性の治療薬の開発につながると期待される。