Elucidation of human pancreatic alpha-cell transdifferentiation mechanism for treatment of diabetes. Search for low molecular weight compounds inhibiting ARX

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09830
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka University
• Principal Investigator: Junji Kozawa 大阪大学, 医学系研究科, 寄附講座准教授 (80513001)
• Co-Investigator(Kenkyū-buntansha): 岩橋 博見 大阪大学, 医学系研究科, 寄附講座准教授 (60397627) ; 福井 健司 大阪大学, 医学系研究科, 助教 (60513009) ; 木村 武量 大阪大学, 医学系研究科, 助教 (70770171)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 膵β細胞 / 膵α細胞 / 分化転換 / 再生療法

Outline of Final Research Achievements

In pancreatic histological analyses in patients who underwent pancreatectomy in Osaka university hospital, pancreatic alpha-cell proliferation and the area ratio of alpha cell/beta cell increased in patients with long-standing type 2 diabetes. The reduced beta-cell mass was associated with the reduced expression of ARX and the increased expression of NKX6.1 in alpha cell. This suggested that the compensation for the reduced beta-cell mass through proliferation and transdifferentiation of alpha cell. In addition, the progression of diabetes intolerance was associated with pancreatic fatty infiltration and islet inflammation.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

本邦において、糖尿病患者は増加の一途を辿り、糖尿病治療薬の開発は進んでいるが、未だ膵β細胞量の減少に対する根治的な治療法は開発されていない。膵α細胞のARXを中心とする転写因子発現変化が膵β細胞への分化転換へつながる可能性、今後の膵α細胞におけるARX発現調節を介した膵β細胞再生療法への組織学的な基盤が示された。