Determinants of pancreatic beta cell vulnerability common to type 1 and type 2 diabetes mellitus.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16419
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kindai University
• Principal Investigator: Taketomo Yasunori 近畿大学, 医学部, 講師 (20580591)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 1型糖尿病 / 2型糖尿病 / インスリン分泌 / HLA

Outline of Final Research Achievements

Multiple regression analysis was performed to examine the determinants of residual insulin secretory capacity in 102 patients with acute onset type 1 diabetes. The duration of disease as a clinical factor and possession of class II HLA genotype, DRB1*04:05-DQB1*04:01/DRB1*09:01-DQB1*03:03 (DR4/DR9), as a genetic factor were extracted as independent determinants. The results suggest an early decline in insulin secretion capacity in DR4/DR9 genotype carriers in acute-onset type 1 diabetes. GLIS3 gene polymorphism, which has been reported to be associated with type 1 and type 2 diabetes in Caucasians, was analyzed in relation to type 1 and type 2 diabetes in Japanese population, but no significant association was observed.

Free Research Field

内分泌代謝

Academic Significance and Societal Importance of the Research Achievements

1型糖尿病と２型糖尿病はいずれも膵β細胞不全による内因性インスリン分泌能低下に基づく病態であることは共通している。膵β細胞不全と最も関連する遺伝因子としてHLA遺伝子、その他の関連遺伝子としてnon HLA遺伝子も多数報告されている。本邦と海外で膵β細胞不全と異なる関連を示すものも存在し、人種別に検討する必要があるものの、1型糖尿病と２型糖尿病に共通する膵β細胞不全を規定する遺伝因子を解明することは、膵β細胞破壊の分子メカニズムを解明し、新たな治療法の開発や病態の進展防止・予知法の開発に資する可能性を秘めている。