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Elucidation of the novel mechanism of the fatty acid-induced pancreatic beta-cell proliferation and its application to diabetes treatment

Research Project

Project/Area Number 18K19724
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

Matsuzaka Takashi  筑波大学, 医学医療系, 教授 (70400679)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsオレイン酸 / リノール酸 / 脂肪毒性 / 糖尿病 / ベータ細胞 / 細胞増殖 / 脂肪酸
Outline of Final Research Achievements

Elucidation of the molecular mechanism of pancreatic beta-cell proliferation is important for the prevention and treatment of type 2 diabetes. The aim of this study is to identify the specific fatty acid(s) that activate bete-cell proliferation. We isolated pancreatic islets from mice and treated with various types of fatty acids. We found that oleic acid (C18:1n-9) and linoleic acid (C18:2n-6) strongly stimulated the proliferation of pancreatic beta-cells. We also found that the activation of these fatty acids within beta-cells was necessary for the proliferation of beta-cells and signalling molecule X was involved in this effect.

Academic Significance and Societal Importance of the Research Achievements

生体における脂肪酸の長期的な投与は膵臓β細胞の増殖を引き起こす一方、場合によっては脂肪毒性を引き起こす可能性があるが「脂肪酸により制御されるβ細胞増殖経路」を選択的にコントロールできれば、脂肪毒性を引き起こすことなく膵臓β細胞量を増加させることが可能となる。本研究の成果は、糖尿病の新しい発症機序の解明や新規糖尿病治療薬の開発に役立つだけではなく、機能性食品の開発、iPS細胞等を利用した再生医療における膵β細胞の効率的な作製への応用も期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 Other

All Journal Article (9 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (3 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] CREBH Improves Diet-Induced Obesity, Insulin Resistance, and Metabolic Disturbances by FGF21-Dependent and FGF21-Independent Mechanisms2020

    • Author(s)
      Satoh Aoi、Han Song-iee、Araki Masaya、Nakagawa Yoshimi、Ohno Hiroshi、Mizunoe Yuhei、Kumagai Kae、Murayama Yuki、Osaki Yoshinori、Iwasaki Hitoshi、Sekiya Motohiro、Konishi Morichika、Itoh Nobuyuki、Matsuzaka Takashi、Sone Hirohito、Shimano Hitoshi
    • Journal Title

      iScience

      Volume: 23 Issue: 3 Pages: 100930-100930

    • DOI

      10.1016/j.isci.2020.100930

    • NAID

      120006891020

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcriptional co-repressor CtBP2 orchestrates epithelial-mesenchymal transition through a novel transcriptional holocomplex with OCT12020

    • Author(s)
      Ma Yang、Sekiya Motohiro、Kainoh Kenta、Matsuda Takaaki、Iwasaki Hitoshi、Osaki Yoshinori、Sugano Yoko、Suzuki Hiroaki、Takeuchi Yoshinori、Miyamoto Takafumi、Yahagi Naoya、Nakagawa Yoshimi、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 523 Issue: 2 Pages: 354-360

    • DOI

      10.1016/j.bbrc.2019.12.070

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl‐Chain Length and Hepatic Insulin Sensitivity in Mice2020

    • Author(s)
      Matsuzaka T、Kuba M、Koyasu S、Yamamoto Y、Motomura K、Arulmozhiraja S、Ohno H、Sharma R、Shimura T、Okajima Y、Han SI、Aita Y、Mizunoe Y、Osaki Y、Iwasaki H、Yatoh S、Suzuki H、Sone H、Takeuchi Y、Yahagi N、Miyamoto T、Sekiya M、Nakagawa Y、Ema M、Takahashi S、Tokiwa H、Shimano H
    • Journal Title

      Hepatology

      Volume: 71 Issue: 5 Pages: 1609-1625

    • DOI

      10.1002/hep.30953

    • NAID

      120007132717

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 脂肪酸による膵β細胞増殖作用2020

    • Author(s)
      本村香織、松坂賢
    • Journal Title

      Medical Science Digest

      Volume: 46(1) Pages: 64-66

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ROCK 1 as a new player in the regulation of hepatic lipogenesis2019

    • Author(s)
      Miyamoto Takafumi、Matsuzaka Takashi、Shimano Hitoshi
    • Journal Title

      Journal of Diabetes Investigation

      Volume: - Issue: 5 Pages: 1165-1167

    • DOI

      10.1111/jdi.13051

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Octacosanol and policosanol prevent high-fat diet-induced obesity and metabolic disorders by activating brown adipose tissue and improving liver metabolism2019

    • Author(s)
      Sharma Rahu, Takafumi Miyamoto, et al.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 5169-5169

    • DOI

      10.1038/s41598-019-41631-1

    • NAID

      120007133465

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation.2018

    • Author(s)
      Nakamura Y, Matsuzaka T, Tahara-Hanaoka S, Shibuya K, Shimano H, Nakahashi-Oda C, Shibuya A.
    • Journal Title

      Cell Death Dis.

      Volume: 9(12) Issue: 12 Pages: 1181-1181

    • DOI

      10.1038/s41419-018-1226-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transgenic Mice Overexpressing SREBP-1a in Male ob/ob Mice Exhibit Lipodystrophy and Exacerbate Insulin Resistance.2018

    • Author(s)
      Ohno H, Matsuzaka T, Tang N, Sharma R, Motomura K, Shimura T, Satoh A, Han SI, Takeuchi Y, Aita Y, Iwasaki H, Yatoh S, Suzuki H, Sekiya M, Nakagawa Y, Sone H, Yahagi N, Yamada N, Higami Y, Shimano H.
    • Journal Title

      Endocrinology.

      Volume: 159(6) Issue: 6 Pages: 2308-2323

    • DOI

      10.1210/en.2017-03179

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Saturated Fatty Acids Undergo Intracellular Crystallization and Activate the NLRP3 Inflammasome in MacrophagesHighlights2018

    • Author(s)
      Karasawa Tadayoshi、Kawashima Akira、Usui-Kawanishi Fumitake、Watanabe Sachiko、Kimura Hiroaki、Kamata Ryo、Shirasuna Koumei、Koyama Yutaro、Sato-Tomita Ayana、Matsuzaka Takashi、Tomoda Hiroshi、Park Sam-Yong、Shibayama Naoya、Shimano Hitoshi、Kasahara Tadashi、Takahashi Masafumi
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 38 Issue: 4 Pages: 744-756

    • DOI

      10.1161/atvbaha.117.310581

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 膵β細胞の増殖を誘導する脂肪酸の探索とその分子機構の解析2019

    • Author(s)
      本村香織、松坂賢、大野博、宮本崇史、関谷元博、中川嘉、島野仁
    • Organizer
      第56回日本臨床分子医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪酸伸長酵素Elovl6による脂肪酸の質の制御と組織内蓄積脂肪2018

    • Author(s)
      松坂賢、島野仁
    • Organizer
      第40回日本臨床栄養学会総会・第39回日本臨床栄養協会総会 第16回大連合大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 脂肪酸の質的変化による脂質代謝、エネルギー代謝2018

    • Author(s)
      松坂賢、島野仁
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] 筑波大学内分泌代謝・糖尿病内科

    • URL

      https://www.u-tsukuba-endocrinology.jp/

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Remarks] 松坂研究室

    • URL

      http://matsuzakalab-tsukuba.org/

    • Related Report
      2019 Annual Research Report 2018 Research-status Report

URL: 

Published: 2018-07-25   Modified: 2021-02-19  

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