Type 2 diabetes mellitus as a periodontitis-related systemic disease and analysis of its pathogenesis mechanism
| Project/Area Number |
19K19005
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57030:Conservative dentistry-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | P.gingivalis / 糖尿病 / DPP4 / P. gingivalis / DDP４ / 歯周炎 |
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| Outline of Research at the Start |
歯周炎は２型糖尿病のリスクファクターと示唆されているものの，その分子機構はいまだ明らかではない．２型糖尿病の病態形成機序の１つとして，ジペプチジルペプチダーゼ4（DPP4）によるインクレチンの不活性化がある．申請者はP. gingivalis をはじめとする複数のヒト慢性歯周炎の主要原因細菌種がDPP4 を保有し，ヒトDPP4同様にインクレチンを切断することを明らかにした．しかし，歯周組織局所の病態が２型糖尿病の病態形成と進行に関わるかは明確ではない．本研究では歯周病原細菌の感染による歯周炎モデルマウスを作製し，局所の歯周病原細菌感染がインクレチン切断に演じる役割について検討する．
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| Outline of Final Research Achievements |
Porphyromonas gingivalis, a Gram-negative anaerobes, is important pathogen associated with chronic periodontitis. And this bacterium is closely related to systemic diseases, such as type 2 diabetes mellitus. We previously demonstrated more direct involvement, as P. gingivalis dipeptidyl-peptidase (DPP)4 was shown to degrade incretin peptides, resulting in elevation and prolongation of postprandial hyperglycemia in a mouse model. In this study, we assessed whether other DPPs could degrade incretins as same as DPP4. P. gingivalis DPP7 has more potent hydrolyzing activity toward incretins and other gastrointestinal peptides than DPP4. In addition, intravenous administration of DPP7 in mice decreased serum levels of active GLP-1 and blood glucose levels. DPP7 was also shown to hydrolyze insulin. In summary, P. gingivalis is important pathogen associated with type 2 diabetes mellitus.
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| Academic Significance and Societal Importance of the Research Achievements |
歯周病原細菌P. gingivalisのDPP4 やDPP7 はインクレチンやインスリンなどの血糖値コントロールにかかわる生理活性物質を切断・不活性化することから，口腔局所に感染しているの本菌の血流への侵入が2型糖尿病の病態形成にかかわることが強く示唆された．以上のことから，歯科処置による口腔内のP. gingivalisの減少は2型糖尿病の予防や病態改善に寄与するものと推察される．
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Report
(4 results)
Research Products
(4 results)
