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

Research Project

Project/Area Number 15K11047
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionNagasaki 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
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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 / 歯周病菌 / エキソペプチダーゼ / インクレチン / インスリン / 耐糖試験 / DPP7 / DPP11 / 糖尿病 / DPP / Prevotera intermedia / Trepanema forsythia / ペプチド代謝 / ジペプチド / アミノ酸トランスポーター / ペプチダーゼ
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.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] Max F. Perutz Laboratories(Austria)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Vienna(Austria)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Vienna(Austria)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Establishment of potent and specific synthetic substrate for dipeptidyl-peptidase 7.2018

    • Author(s)
      Nemoto TK, Ono T, Ohara-Nemoto Y.
    • Journal Title

      Anal Biochem

      Volume: 548 Pages: 78-81

    • DOI

      10.1016/j.ab.2018.02.008

    • NAID

      120006987355

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a new subtype of dipeptidyl peptidase 11 and a third group of the S46-family members specifically present in the genus Bacteroides.2018

    • Author(s)
      Nemoto TK, Bezerra GA, Ono T, Nishimata H, Fujiwara T, Ohara-Nemoto Y.
    • Journal Title

      Biochimie

      Volume: 147 Pages: 25-35

    • DOI

      10.1016/j.biochi.2017.10.015

    • NAID

      120006987398

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4.2017

    • Author(s)
      Ohara-Nemoto, Y., Nakasato, M., Shimoyama, Y., Baba, T., Kobayakawa, T., Ono, T., Yaegashi, T., Kimura, S., Nemoto, T.K.
    • Journal Title

      Infection and Immunity

      Volume: 85 Issue: 9

    • DOI

      10.1128/iai.00277-17

    • NAID

      120006987494

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bacterial protease uses distinct thermodynamic signatures for substrate recognition.2017

    • Author(s)
      Bezerra, G. A., Ohara-Nemoto, Y., Fedosyuk, S., Cornaciu, I., Hoffmann, G., Round, A., Marquez, J. A., Nemoto, T.K., Djinovic-Carugo, K.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 2848-2848

    • DOI

      10.1038/s41598-017-03220-y

    • NAID

      120006987515

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dominant prevalence of Porphyromonas gingivalis fimA types I and IV in healthy Japanese children.2017

    • Author(s)
      Shimoyama Y, Ohara-Nemoto Y, Kimura M, Tanaka M, Kimura S, and Nemoto TK.
    • Journal Title

      J Dent Sci.

      Volume: 印刷中 Issue: 3 Pages: 213-219

    • DOI

      10.1016/j.jds.2017.03.006

    • NAID

      120006987517

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Skp2 regulates the expression of MMP-2 and MMP-9, and enhances the invasion potential of oral squamous cell carcinoma.2016

    • Author(s)
      Yamada SI, Yanamoto S, Naruse T, Matsushita Y, Takahashi H, Umeda M, Nemoto TK, and Kurita H.
    • Journal Title

      Pathol Oncol Res.

      Volume: 52 Issue: 3 Pages: 22-29

    • DOI

      10.1007/s12253-016-0049-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Porphyromonas gingivalis periplasmic novel exopeptidase, acylpeptidyl oligopeptidase, releases N-acylated di- and tri-peptides from oligopeptides.2016

    • Author(s)
      Nemoto, T.K., Ohara-Nemoto, Y., Bezerra, G. A., Shimoyama, Y. and Kimura, S.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 11 Pages: 5913-5925

    • DOI

      10.1074/jbc.m115.687566

    • NAID

      120006986807

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Porphyromonas gingivalis exopeptidases as crucial factors for its amino acid metabolism2016

    • Author(s)
      Nemoto, T.K., Ohara-Nemoto, Y.
    • Journal Title

      Jap. Dent. Sci. Rev.

      Volume: 52 Issue: 1 Pages: 22-29

    • DOI

      10.1016/j.jdsr.2015.08.002

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Skp2 regulates the expression of MMP-2 and MMP-9, and enhances the invasion potential of oral squamous cell carcinoma.2016

    • Author(s)
      Yamada, SI, Yanamoto S, Naruse T, Matsushita Y, Takahashi H, Umeda M, Nemoto TK, and Kurita H.
    • Journal Title

      Pathol Oncol Res.

      Volume: 52

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Bacteroides 属菌が有する S46 ファミリージペプチジ ルペプチダーゼ2017

    • Author(s)
      根本 優子, 小野 俊雄, 根本 孝幸
    • Organizer
      第90回日本細菌学会
    • Place of Presentation
      仙台国際センター (宮城県仙台市)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Bacteroides属菌が有するS46ファミリージペプチジルペプチダーゼ. (S46 family dipeptidyl peptidases (DPPs) in the genus Bacteroides)2017

    • Author(s)
      根本優子,小野俊雄,根本孝幸
    • Organizer
      第90回日本細菌学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Porphyromonas gingivalis および Tannerella forsythia のジペプチジルペプチダーゼ4 活性とインクレチン分解能2017

    • Author(s)
      中里茉那美,根本優子,下山佑,木村重信,佐々木大輔,伊東俊太郎,佐々木実,八重柏隆
    • Organizer
      第60回春季日本歯周病学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 歯周病原性細菌アシルペプチジルオリゴペプチダーゼ(AOP)のアシルペプチド選択機構.(Acylpeptide recognition mechanism of acylpeptidyl oligopeptidase in periodontopathic bacteria)2017

    • Author(s)
      根本孝幸,小野俊雄,根本優子
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Porphyromonas gingivalisのアミノ酸及びオリゴペプチド輸送系の解析 (Amino acid and oligopeptide transporters in Porphyromonas gingivalis)2016

    • Author(s)
      根本優子,小早川健,馬場友巳,根本孝幸
    • Organizer
      第58回歯科基礎医学会学術大会・総会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 小児プラークにおけるミュータンスレンサ球菌定着量と齲蝕罹患率の関連 (Quantification of mutans streptococci in children’s plaques and its relationship to the caries prevalence).2016

    • Author(s)
      蒔苗 剛, 下山 佑, 田中光郎,石河太知, 古玉芳豊, 佐々木 実, 根本優子, 根本孝幸, 木村重信
    • Organizer
      第58回歯科基礎医学会学術大会・総会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Degradation of incretin by the prokaryotic dipeptidyl-peptidase 4 from Porphyromonas gingivalis.2016

    • Author(s)
      Shimoyama Y, Ohara-Nemoto Y, Nemoto TK, Nakasato M, Yaegashi T, Ishikawa T, Sasaki M, Kimura S
    • Organizer
      ASM 2016 General meeting
    • Place of Presentation
      ボストン (アメリカ)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of dipeptidyl-peptidase 4 from Tannerella forsythia.2016

    • Author(s)
      Nakasato M, Shimoyama Y, Ohara-Nemoto Y, Nemoto TK, Takahashi S, Ito S, Sasaki D, Yaegashi T, Kimura S
    • Organizer
      ASM 2016 General meeting
    • Place of Presentation
      ボストン (アメリカ)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Djinovic-Carugo K: Porphyromonas sp. dipeptidyl peptidases 11 distinguish substrates from end products via distinct thermodynamic signatures.2016

    • Author(s)
      Bezerra GA, Ohara-Nemoto Y, Fedosyuk S, Cornaciu I, Hoffmann G, Marquez JA, Nemoto TK,
    • Organizer
      EMBO Conference The biochemistry and chemistry of biocatalysis: From understanding to design
    • Place of Presentation
      オウル (フィンランド)
    • Year and Date
      2016-06-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] アシルオリゴペプチジルペプチダーゼ活性を有する歯周病原性細菌の新規ペプチダーゼ2015

    • Author(s)
      根本孝幸,根本優子
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟市、朱鷺メッセ
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 非RI蛍光試薬によるPorphyromonas gingivalisのアミノ酸とジペプチドの取り込みの評価2015

    • Author(s)
      小早川健,根本優子,馬場友巳,根本孝幸
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟市、朱鷺メッセ
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 2種類のビスフォスフォネートの骨芽細胞におけるアルカリフォスファターゼ活性 および基質形成に対する異なる効果2015

    • Author(s)
      馬場友巳,宮崎敏博,根本優子,根本孝幸
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟市、朱鷺メッセ
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Tannerella forsythia のジペプチジルペプチダーゼ4の性状解析2015

    • Author(s)
      中里茉那美,下山佑,根本優子,根本孝幸,高橋晋平,石河太知,佐々木実,八重柏隆,木
    • Organizer
      第57回歯科基礎医学会学術大会・総会
    • Place of Presentation
      新潟市、朱鷺メッセ
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 歯周病原性‘red complex species’のビルレンス因子としてのプロテアーゼ2015

    • Author(s)
      下山佑,中里茉那美,根本優子,根本孝幸,石河太知,八重柏隆,佐々木実,木村重信
    • Organizer
      日本細菌学会東北支部総会
    • Place of Presentation
      郡山市、郡山ビッグアイ
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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