Investigation into the pathogenic mechanism of type 2 diabetes focusing on Paneth cell alpha-defensins

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K19610
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58060:Clinical nursing-related
• Research Institution: Sapporo University of Health Sciences
• Principal Investigator: Kato Takatoshi 札幌保健医療大学, 保健医療学部, 講師 (00756421)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: パネート細胞 / αディフェンシン / 腸内細菌叢 / ２型糖尿病 / 過食

Outline of Final Research Achievements

The purpose of this study was to reveal the pathogenic mechanism of type 2 diabetes mellitus(T2DM) which was involved in Paneth cell α-defensins.
This study analyzed secreted α-defensins levels and the intestinal microbiota using the db/db mice which was the animal model of T2DM. Consequently, secreted α-defensins levels were reduced with increase of the blood glucose levels, and the intestinal microbiota showed significantly different β- diversity. Furthermore, this intervention study of the dietary restriction in db/db mice show that the dietary restriction suppressed the decrease of α-defensins, maintained the amount of α-defensins at the start of experiment, and decreased the blood glucose levels.
Therefore, this report suggests the pathogenic mechanism of T2DM which mediated via dysbiosis of the intestinal microbiota along with the reduction in Paneth cell α-defensins through the overeating.

Free Research Field

慢性看護

Academic Significance and Societal Importance of the Research Achievements

わが国では糖尿病患者数は約 2050万人(可能性の者を含める)と推計され、この15年間で約680万人増加している。糖尿病は三大合併症をはじめ種々の血管疾患を併発させることから患者の生活の質を低下させ、国民医療費も増大させることから非常に深刻な問題であり、新たな発症メカニズムを解明する必要がある。
本研究は過食によるPaneth細胞α-defensinの分泌量低下に伴う腸内細菌叢のdysbiosisを介した2型糖尿病発症メカニズムの可能性が示唆された。
本研究はわが国および世界で急増している2型糖尿病の新たな治療戦略や発症予防を検討する基盤となり得るものであり、社会的意義は大きいと考える。