Investigation of the mechanism of immune function reduction by diabetes mellitus

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17799
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Kindai University
• Principal Investigator: KITAURA Atsuhiro 近畿大学, 医学部, 助教 (20716485)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖化最終産物 / 糖尿病 / 免疫 / マクロファージ

Outline of Final Research Achievements

Diabetes mellitus causes a decrease in immunity, leading to the development of infections and worsening prognosis. To understand the mechanism of immunocompromised immunity caused by diabetes, we focused on a substance called advanced glycation end products (AGEs), which are highly bioactive and are produced and accumulated after prolonged exposure to high blood glucose. AGEs have various effects on the immune system. Among them, we investigated the effects on the activity of macrophages, which are an important command post of the immune system. As a result, we found that AGEs suppress the normal immune response to bacteria by inhibiting the uptake of an inflammation-producing substance called lipopolysaccharide (LPS), which is derived from Gram-negative rods, into macrophages.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、糖化最終産物（AGEs）が、マクロファージのエンドサイトーシス抑制と、その下流経路にあたるマクロファージのサイトカイン分泌抑制を明らかにした。糖化最終産物は免疫系の中で中心的役割を担うマクロファージの機能を抑制する。本研究によって、糖尿病の免疫低下における新たなメカニズムを明らかにしたことは、in vitro 研究でまだ臨床応用にはほど遠いが、今後の糖尿病管理および糖尿病合併症管理において、新たな治療ターゲットを提供する可能性がある。糖尿病は日本でも有病率が高く、また脳血管疾患や血液透析の最も強い誘因となりうるので、もし将来的に臨床応用がかなった場合には、その波及効果は大きい。