The role of inflammatory induced Xaf1 in pancreatic beta cells~correlation with periodontitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10152
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Iwashita Misaki 九州大学, 歯学研究院, 助教 (80611326)
• Co-Investigator(Kenkyū-buntansha): 浅野 知一郎 広島大学, 医系科学研究科(医), 教授 (70242063) ; 西村 英紀 九州大学, 歯学研究院, 教授 (80208222)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 膵β細胞 / XAF1 / アポトーシス

Outline of Final Research Achievements

We explored the effects of X-linked inhibitor of apoptosis associated factor 1 (XAF1) on β-cell function and progression of diabetes in vivo. Pancreatic β-cell-specific XAF1 overexpressing (Xaf1 Tg) mice and their wild-type (WT) littermates were fed either a normal diet or a high-fat diet (HFD).
HFD-fed Xaf1 Tg mice demonstrated increased β-cell apoptosis, lowered insulin expression, and impaired glucose tolerance compared with WT mice fed the same diet. Pancreatic β-cell XAF1 expression was enhanced via HFD-induced, macrophage-derived interferon β (IFNβ), which promoted β-cell apoptosis and led to a reduction in insulin secretion and progression of diabetes. Since bacterial endotoxin also stimulates IFNβ production from macrophages, it may indicate an association between low-grade inflammation-induced pancreatic β-cell XAF1 expression and exacerbation of diabetes, thus providing insight into the mechanism of β-cell mass reduction in diabetes.

Free Research Field

歯周病学

Academic Significance and Societal Importance of the Research Achievements

肥満状態では、脂肪組織等でマクロファージが活性化し糖尿病を増悪させる炎症が持続していることが以前から知られていた。本研究ではそれに加えて、活性化マクロファージ誘導性のXAF1発現の増大が膵β細胞のアポトーシス亢進を引き起こすことで糖尿病の増悪に関与することが示された。
本研究結果は、糖尿病の根本的治療の鍵である膵β細胞量減少のメカニズムの解明と、インスリン分泌能の低下しやすい日本人糖尿病患者に対する新たな治療戦略の基盤となりうる。