The possible role of insulin resistance in vascular endothelial cells on exacerbation of periodontitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18513
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Shinjo Takanori 九州大学, 歯学研究院, 助教 (20711394)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 糖尿病関連歯周炎 / インスリン抵抗性 / 血管内皮細胞 / VCAM1 / FoxO1

Outline of Final Research Achievements

We found that LPS and TNFa-induced VCAM1 expression was significantly suppressed by insulin pretreatment via PI3K-Akt-FoxO1 pathway in TKD2 cells. Insulin resistance was induced by culturing under high glucose for 48 hours. Hyperglycemia-treated TKD2 cells showed less insulin action on LPS and TNFa-induced VCAM1 expression. Cell adhesion between TKD2 and THP-1 cells was regulated by insulin dependent on VCAM1 expression in TKD2 cells.
Animal studies revealed that insulin receptor expression was decreased by 50%, and phosphorylation of Akt-FoxO1 pathway was suppressed in the gingiva of VEIRKO mice compared to those of WT mice under ex vivo insulin treatment. Experimental periodontitis was more exacerbated in VEIRKO mice than WT mice.

Free Research Field

歯周病学

Academic Significance and Societal Importance of the Research Achievements

今回、歯肉構成細胞の一つである血管内皮細胞でのインスリン作用が感染性炎症によるVCAM1発現を制御しており、肥満や糖尿病などインスリン抵抗性が生じる環境下ではこの制御が破綻し、結果的に歯周炎が増悪することを見出した。この発見は、歯周組織におけるインスリン抵抗性が糖尿病関連歯周炎の病態基盤に重要な役割を持つことを示唆するものであり、学術的意義は大きい。さらに、歯肉局所のインスリン感受性の回復が歯周炎の進行抑制や治癒の促進に有用であることを示唆するものでもあり、新規治療法の開発に資すると考えられ、社会的意義も大きい。