Investigation of regulatory mechanisms for glucose metabolism through metabolic pathway of kynurenic acid

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08871
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyorin University
• Principal Investigator: Gotoda Takanari 杏林大学, 医学部, 教授 (60322062)
• Co-Investigator(Kenkyū-buntansha): 山本 隆史 杏林大学, 医学部, 学内講師 (00572033)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: キヌレン酸 / 糖代謝 / ノックアウトマウス

Outline of Final Research Achievements

Metabolic syndrome is a pathological condition characterized by the coexistence of diabetes (impaired glucose metabolism), hypertension and dyslipidemia in an individual with visceral obesity. We have previously reported a correlation between abnormality in the synthetic enzyme for kynurenic acid (KAT), a metabolite of tryptophan, and metabolic syndrome-like phenotypes in an animal model. Upon the present further investigation, we found that KAT-deficient mice, which exhibited decreased levels of kynurenic acid, display a phenotype resembling diabetes mellitus. Conversely, it has been shown that the manipulation that increases the levels of kynurenic acid in mice improves the symptoms of obesity-induced diabetes. This study has revealed a new aspect of kynurenic acid metabolism, highlighting its involvement in the regulation of glucose metabolism.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

トリプトファンの代謝物であるキヌレン酸は、うつや統合失調症といった精神疾患との関連が報告されてきたが、メタボリックシンドロームとの関連に関してはわれわれが遺伝解析により独自に見出した知見以外には報告されていない。今回の研究結果はこの知見をさらに発展させるものであり、キヌレン酸代謝系への介入により糖代謝異常やメタボリックシンドロームを改善する可能性を示すものである。