Exopeptidases from periodontopathic bacteria as risk factors of type-2 diabetes mellitus

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K11047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Nagasaki University
• Principal Investigator: NEMOTO Takayuki 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (90164665)
• Co-Investigator(Kenkyū-buntansha): 小早川 健 長崎大学, 医歯薬学総合研究科(歯学系), 技術職員 (10153587) ; 根本 優子 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10164667) ; 木村 重信 関西女子短期大学, 歯科衛生学科, 教授 (10177917) ; 馬場 友巳 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (60189727) ; 下山 佑 岩手医科大学, 歯学部, 講師 (90453331)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 歯周病 / 歯周病細菌 / ジペプチジルペプチダーゼ / プロテアーゼ / Porphyromonas gingivalis

Outline of Final Research Achievements

We previously identified novel exopeptidases expressed in periodontopathic bacteria, such as Porphyromonas gingivalis. In this project, we synthesized a substrate truly specific for dipeptidyl-peptidase (DPP) 7. Moreover, based on the hypothesis that these exopeptidases are involved to the exacerbation of type-2 diabetes melitus, we investiagetd the role of bacterial DPPs.
Mice with pre-injected with DPP4 showed increased blood glucose concentrations and retarded decline during the glucose tolerance test. In consistent to these changes, blood insulin and incretin (GLP-1) concentrations were decresed in DPP4-injected mice. To our knowledge, this is the first study that periodontopathic bactria can exacerbate type-2 diabetes via bacterial DPP4.
Separately, we identified an oligopeptidase in P. gingivalis that preferentially degrades N-terminally acylated peptides, which are unable to be degraded by DPPs.

Free Research Field

口腔生化学