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Prevention and improvement of type 2 diabetes by DPP-4 inhibitory peptides found in fermented mushroom milk

Research Project

Project/Area Number 19K11691
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionTottori University

Principal Investigator

Kenji Okamoto  鳥取大学, 工学研究科, 教授 (80283969)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsDPP-4阻害ペプチド / 食用きのこ / Flammulina velutipes / Grifola frondosa / 発酵 / イソフラボン / エルゴチオネイン / 発酵乳 / 高血糖 / インクレチン / DPP-4 / ペプチド / きのこ
Outline of Research at the Start

わが国の糖尿病患者数は急速に増加しており、高血糖の状態を放置すると網膜症・腎症・神経障害など重篤な合併症を引き起こすほか、特に高齢糖尿病患者は認知症をおこしやすく、少子高齢化社会において血糖値コントロールはより重要となる。申請者は牛乳をきのこで発酵させるという新たな技術で、発酵乳中に2型糖尿病治療薬のターゲットとされるDPP-4(Dipepeptidyl peptidase-4)に有効な阻害活性を見いだした。本研究では、発酵乳中の活性ペプチドの単離、ペプチド発酵生産技術の開発、酵素系の解明、生体内での効果を調査し、高血糖対象の新しい機能性食品素材として展開するための基盤技術を確立する。

Outline of Final Research Achievements

Edible mushrooms Flammulina velutipes and Grifola frondosa were grown in milk or soymilk, and it was clarified that the DPP-4 inhibitory peptide involved in blood glucose suppression was specifically accumulated.
When fermented soymilk with F. velutipes was administered to mice fed a high-fat diet, it showed a tendency to moderate the increase in postprandial blood glucose level.
On the other hand, in the fermentation process of soymilk, conversion to isoflavone aglycone, which is well absorbed in the body, was observed. In addition, fermented soymilk was found to have antioxidant activity, and the main component was identified as ergothioneine.

Academic Significance and Societal Importance of the Research Achievements

本研究では2型糖尿病治療のターゲットの一つとされるDPP-4阻害に着目し、身近な食用きのこを牛乳や豆乳を原料に生育させることでDPP-4阻害活性を示すペプチドの効率的な遊離を見いだした。発酵豆乳には食後血糖値の上昇を穏やかにする傾向が示唆された。
さらに、体内吸収性が高いイソフラボンアグリコンや抗酸化物質の存在も明らかになるなど、生活習慣病の予防と健康維持に関わる新たな食素材への応用が期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (8 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Milk Fermented with Mushrooms Prevents Stroke in the Stroke-Prone Spontaneously Hypertensive Rats Independently of Blood Pressure2022

    • Author(s)
      Mahal Zinat、Matsuo Hiroyuki、Zahid Hasan M.、Notsu Yoshitomo、Ohara Hiroki、Okamoto Kenji、Nabika Toru
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 31 Issue: 5 Pages: 106421-106421

    • DOI

      10.1016/j.jstrokecerebrovasdis.2022.106421

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct ethanol production from xylan and acorn using the starch-fermenting basidiomycete fungus Phlebia acerina2021

    • Author(s)
      Okamoto Kenji, Goda Takato, Yamada Takeru, Nagoshi Masafumi
    • Journal Title

      Fermentation

      Volume: 7 Issue: 3 Pages: 116-116

    • DOI

      10.3390/fermentation7030116

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of the antihypertensive peptide Tyr-Pro from milk using the white-rot fungus Peniophora sp. in submerged fermentation and a jar fermentor2021

    • Author(s)
      Okamoto Kenji, Ito Ryosuke, Hayashi June, Tagawa Mizuki
    • Journal Title

      Dairy

      Volume: 2 Issue: 3 Pages: 452-461

    • DOI

      10.3390/dairy2030036

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of an antihypertensive peptide from milk by the brown rot fungus Neolentinus lepideus2020

    • Author(s)
      Okamoto Kenji、Kawamura Sayo、Tagawa Mizuki、Mizuta Toshifumi、Zahid Hasan M.、Nabika Toru
    • Journal Title

      European Food Research and Technology

      Volume: 246 Issue: 9 Pages: 1773-1782

    • DOI

      10.1007/s00217-020-03530-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 食用きのこ発酵乳由来のDPP-4阻害ペプチド2020

    • Author(s)
      岡本賢治
    • Journal Title

      アグリバイオ

      Volume: 4 Pages: 54-55

    • Related Report
      2020 Research-status Report
  • [Presentation] 白色腐朽菌の牛乳発酵による機能性ペプチドの生産2019

    • Author(s)
      伊藤諒祐, 林寿音, 安藤彰悟, 並河徹, 岡本賢治
    • Organizer
      日本農芸化学会2019年度西日本・中四国支部合同沖縄大会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] ジペプチジルペプチダーゼⅣ阻害活性が高い発酵乳およびその製造方法2020

    • Inventor(s)
      岡本賢治
    • Industrial Property Rights Holder
      鳥取大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] ジペプチジルペプチターゼⅣ阻害活性が高い豆類発酵物およびその製造方法2019

    • Inventor(s)
      岡本賢治
    • Industrial Property Rights Holder
      岡本賢治
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-225717
    • Filing Date
      2019
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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