Development of new prophylactic treatment for type 1 diabetes by controlling intracellular metabolism targeting immune cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kobe University
• Principal Investigator: YASUDA HISAFUMI 神戸大学, 保健学研究科, 教授 (50403233)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 1型糖尿病 / 免疫細胞 / 細胞内代謝 / 免疫代謝 / AMPK / 解糖系

Outline of Final Research Achievements

Our preliminary experiments in type 1 diabetes (T1D) model mice showed that in the state of suppressing the onset of T1D, activation of mTOR signal (glycolysis enhancement, energy consumption enhancement) is suppressed and AMPK activation is rather induced in immune cells, finally leading to glycolysis inhibition, oxidative phosphorylation enhancement and energy production. Based on the results of our experiments, we conducted an administration of an AMPK activator (glycolytic inhibitor) to T1D model mice. As a result, it suppressed the onset of T1D and histologically suppressed insulitis. Flow cytometric analysis of splenocytes revealed a reduction in activated CD4-positive T cells (Teff), CD8-positive T cells and an increase in regulatory T cells (Treg). Taken together, we found that the shift of T cell balance from Teff to Treg is much effective in T1D suppression, suggesting that an AMPK activator (glycolytic inhibitor) would be useful agent of T1D prophylaxis.

Free Research Field

1型糖尿病

Academic Significance and Societal Importance of the Research Achievements

本研究は、1型糖尿病(T1D)発症に関わる免疫細胞の代謝状態に焦点をあて、自然免疫と獲得免疫の橋渡しをする樹状細胞(DC)および発症に関わるT細胞の代謝状態とT1D発症との関連を検討した。また、免疫細胞の細胞内代謝を制御することで免疫細胞機能を制御し、ヒトT1D に対する新規予防的治療法としての「免疫代謝療法」の開発を目指したものであった。本研究の結果は、T1D発症の制御の可能性を広げ、かつ将来のT1Dによる合併症を未然に防ぐこととなり、平均寿命と健康寿命の延伸に繋がるという点で、大変有意義な研究成果であると考えている。