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Elucidation of gastrointestinal motility disorders caused by dietary obesity and of new treatment development

Research Project

Project/Area Number 18K17945
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Satoshi Shimo  健康科学大学, 健康科学部, 准教授 (80734607)

Project Period (FY) 2018-04-01 – 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords糖尿病 / 肥満 / 糖尿病自律神経障害 / 消化管運動障害 / アウエルバッハ神経叢 / 筋間神経叢 / SBF-SEM / 3次元再構築 / 高脂肪食
Outline of Final Research Achievements

Obesity induced in mice through high fat diet (HFD) revealed the following three points. (1) In HFD-fed mice, NOS, substance P, and calbindin in the myenteric plexus were significantly decreased, while NOS was increased after phlorizin treatment. (2) In HFD-fed mice, accumulation of synaptic vesicles in axon varicosities was decreased, but increased synaptic accumulation vesicle and formation of lateral branches were observed after phlorizin treatment. (3) Delayed gastrointestinal transit time was observed in HFD-fed mice. The HFD induced a decrease in synaptic vesicles in the myenteric plexus during the prediabetic period, when glucose intolerance began. Furthermore, it was suggested that phlorizin treatment may act to improve peristalsis as well as restore lost axonal varicosities of the myenteric plexus in HFD-fed obese mice.

Academic Significance and Societal Importance of the Research Achievements

世界の肥満人口は急速に増えており、日本でも欧米型(高脂肪)の食事とともに、肥満を背景とした2型糖尿病患者が増加傾向であり、大きな社会的問題となっている。また、糖尿病の合併症ではしびれなどの感覚神経障害以外にも、下痢や便秘などの消化器症状を高頻度で引き起こし、日常生活が著しく制限されるため社会的な損失も大きい。しかし、これらの消化器症状の発症機序は不明な点が多く、対症的な治療となるため新規薬剤の開発が求められている。我々の研究により、腸管神経叢を標的とした消化管機能改善薬を開発することができれば、糖尿病の新たな治療法として臨床への応用・発展が大いに期待でき、社会的意義は大きい。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (9 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] Department of Anatomy/Faculty of Medicine/University of Medicine and Pharmacy(ベトナム)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Department of Hist. Emb. Genetics/Faculty of Basic Medical Sciences/Pham Ngoc Thach University of Medicine(ベトナム)

    • Related Report
      2020 Research-status Report
  • [Journal Article] High-Fat Diet and Age-Dependent Effects of IgA-Bearing Cell Populations in the Small Intestinal Lamina Propria in Mice2021

    • Author(s)
      Sakamoto Yuta、Niwa Masatoshi、Muramatsu Ken、Shimo Satoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1165-1165

    • DOI

      10.3390/ijms22031165

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium-glucose co-transporter (SGLT) inhibitor restores lost axonal varicosities of the myenteric plexus in a mouse model of high-fat diet-induced obesity2020

    • Author(s)
      Satoshi Shimo, Sei Saitoh, Huy Bang Nguyen, Truc Quynh Thai, Masako Ikutomo, Ken Muramatsu, Nobuhiko Ohno
    • Journal Title

      Scientific Reports

      Volume: 10: 12372. Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-020-69256-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two Diverse Hemodynamic Forces, a Mechanical Stretch and a High Wall Shear Stress, Determine Intracranial Aneurysm Formation.2019

    • Author(s)
      Koseki H, Miyata H, Shimo S, Ohno N, Mifune K, Shimano K, Yamamoto K, Nozaki K, Kasuya H, Narumiya S, Aoki T.
    • Journal Title

      Transl Stroke Res.

      Volume: Epub ahead of print Issue: 1 Pages: 1-13

    • DOI

      10.1007/s12975-019-0690-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved Serial Sectioning Techniques for Correlative Light-Electron Microscopy Mapping of Human Langerhans Islets2018

    • Author(s)
      Saitoh S, Ohno N, Saitoh Y, Terada N, Shimo S, Aida K, Fujii H, Kobayashi T, Ohno S.
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 51 Issue: 1 Pages: 9-20

    • DOI

      10.1267/ahc.17020

    • NAID

      130006405037

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 高脂肪摂取マウスにおける小腸粘膜固有層に分布するIgA陽性細胞の経時的変化2021

    • Author(s)
      坂本祐太, 志茂聡, 村松憲, 丹羽正利
    • Organizer
      第81回日本解剖学会中部支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 高脂肪食摂取下での腸管筋間神経叢における神経伝達物質局在の免疫組織学的検討2021

    • Author(s)
      志茂聡, 坂本祐太, 甘利貴志, 村松憲, 大野伸彦
    • Organizer
      第62回日本組織細胞化学会総会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Sodium-glucose co-transporter (SGLT) inhibitor restores lost axonal varicosities of the myenteric plexus in a mouse model of high-fat diet-induced obesity2020

    • Author(s)
      S Shimo, S Saitoh, HB Nguyen, TQ Thai, M Ikutomo, K Muramatsu, N Ohno
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Immunohistochemical analysis of soluble immunoglobulins in the intestinal mucosa using high-fat feeding model mice2020

    • Author(s)
      Y Sakamoto, S Shimo, K Muramatsu, M Niwa
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 高脂肪食摂取下でのフロリジン投与がアウエルバッハ神経叢に与える影響2019

    • Author(s)
      志茂聡,齊藤成,Huy Bang Nguyen,Truc Quynh Thai,生友聖子,村松憲,大野伸彦
    • Organizer
      第79回日本解剖学会中部支部学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 高脂肪摂食モデルマウスを用いた腸管粘膜内血清蛋白の免疫組織化学的解析2019

    • Author(s)
      坂本祐太,志茂聡,村松憲,丹羽正利
    • Organizer
      第79回日本解剖学会中部支部学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Three-dimensional ultrastructure of myenteric plexus in high-fat diet mice assessed by serial block face scanning electron microscopy.2018

    • Author(s)
      Shimo S, Saitoh S, Nguyen HB,Thai TQ, Muramatsu K, Ohno N.
    • Organizer
      第74回日本顕微鏡学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Correlative light-electron microscopy mapping of Human Langerhans Islets.2018

    • Author(s)
      Saitoh S, Ohno N, Saitoh Y, Terada N, Shimo S, Aida K, Fujii H, Kobayashi T. Ohno S.
    • Organizer
      第74回日本顕微鏡学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] SGLT inhibitor and Impaired Phospholipid Metabolism of Proximal Tubular Epithelium in Diet-Induced Obesity (DIO) Mouse Kidney.2018

    • Author(s)
      Saitoh S,Takaki T, Shimo S, Ohno N.
    • Organizer
      第78回日本解剖学会中部支部学術集会
    • Related Report
      2018 Research-status Report
  • [Book] 組織細胞化学2018-組織細胞化学の基礎から最先端まで:形を観て、機能を識る-2018

    • Author(s)
      大野伸彦,東森生,藤原研,齊藤百合花,志茂聡
    • Total Pages
      14
    • Publisher
      日本組織細胞化学会
    • ISBN
      9784906514939
    • Related Report
      2018 Research-status Report
  • [Remarks] 健康科学大学教員紹介

    • URL

      https://www.kenkoudai.ac.jp/professor/540/

    • Related Report
      2020 Research-status Report
  • [Remarks]

    • URL

      https://www.kenkoudai.ac.jp/modules/waffle0/index.php?t_m=ddcommon_view&id=28&t_dd=waffle0_data2

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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