2023 Fiscal Year Final Research Report

Genetic basis of and biomarker for complete destruction of beta-cells in type 1 diabetes

Research Project

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Project/Area Number	21K08589
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	Kindai University
Principal Investigator	Ikegami Hiroshi 近畿大学, 医学部, 名誉教授 (20221062)
Co-Investigator(Kenkyū-buntansha)	馬場谷成近畿大学, 医学部, 講師 (10449837) 武友保憲近畿大学, 医学部, 講師 (20580591) 廣峰義久近畿大学, 医学部, 講師 (30460851) 能宗伸輔近畿大学, 医学部, 准教授 (90460849)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	１型糖尿病 / 遺伝因子 / ゲノムワイド関連解析 / メタボローム解析 / バイオマーカー / 膵β細胞 / 完全廃絶
Outline of Final Research Achievements	Genetic basis of and biomarkers for complete destruction of pancreatic beta-cells was studied to obtain basic information of complete destruction of beta-cells to establish effective methods for prevention and intervention of type 1 diabetes. Several loci with genome-wide significance were identified by the genome-wide association study (GWAS). Metabolome analysis in peripheral blood identified several metabolites discriminating acute vs chronic phases and complete abolishment vs minimal residual function of beta cells. In particular, hypotaurine was found to be a biomarker of ongoing beta-cell destruction in acute phase of type 1 diabetes. Hypotaurine is an intermediate metabolite in taurine synthesis, whose key enzyme, CSAD, was identified as a gene for fulminant type 1 diabetes by GWAS, indicating that the same taurine synthesis pathway identified through different approach, GWAS and metabolome analysis, is a promissive target for prevention and intervention of type 1 diabetes.
Free Research Field	糖尿病学
Academic Significance and Societal Importance of the Research Achievements	膵β細胞の完全廃絶に関与する遺伝子座やバイオマーカーの同定は、完全廃絶の分子メカニズムの解明という極めて高い学術的意義を有するとともに、膵β細胞完全廃絶の予知・予防・阻止法の標的となる分子・パスウェイを提示することから、膵β細胞の保護・機能保持を通じて、1型糖尿病の根治につながる極めて高い社会的意義を有する。具体的には、同定した新規遺伝子CSADとヒト末梢血メタボローム解析で同定したβ細胞破壊の急性期バイオマーカーHypotaurineは同じタウリン合成系の鍵酵素と中間代謝産物であることから、タウリン合成系が膵β細胞破壊の阻止における重要な標的であることを示している。