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Comprehensive analysis of the mechanisms of pancreatic beta cell proliferation by vagal nerve signals for therapeutic application

Research Project

Project/Area Number 18K16221
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionTohoku University

Principal Investigator

Izumi Tomohito  東北大学, 大学病院, 助教 (80747064)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords迷走神経 / 膵β細胞 / 肝臓 / 再生医療 / 自律神経 / 臓器間ネットワーク / 糖尿病 / 肥満症
Outline of Final Research Achievements

In this project, we explored the molecular mechanisms of vagal nerve signal-mediated cell proliferation and organ regeneration and its therapeutic potential in pancreatic beta cells and the liver. First, we applied a tissue-clearing technology to the pancreas in order to analyze the anatomy of the vagal nerve system within the pancreas. We found that many of intra-pancreatic parasympathetic ganglia are located in the vicinity of islets. Next, we tested whether vagal nerve signals could induce beta cell proliferation in aged animals, in which cell proliferation capacity is known to be severely restricted. We found that high fat diet feeding promoted beta cell proliferation and increased beta cell mass through vagal nerve signals even in aged mice. Moreover, we clarified that vagal nerve signals are critically involved in liver regeneration after partial hepatectomy and elucidated the molecular mechanism by which vagal nerve signals induce hepatocyte proliferation.

Academic Significance and Societal Importance of the Research Achievements

本研究では、研究代表者が所属するグループが見出した神経シグナルを介した細胞増殖誘導機構と、それによる生体の恒常性維持機構の詳細について、膵β細胞と肝臓を用いて明らかにした。神経シグナルによる細胞増殖機構を臨床に応用することで、高齢者に多い膵β細胞が減少することで発症する糖尿病や、肝臓切除後の肝不全などに対する有望な予防、治療法の開発につながることが期待される。

Report

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

    (5 results)

All 2019 2018

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

  • [Journal Article] Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report2019

    • Author(s)
      Kaneko K, Satake C, Izumi T, Tanaka M, Yamamoto J, Asai Y, Sawada S, Imai J, Yamada T, Katagiri H.
    • Journal Title

      BMC Endocr Disord.

      Volume: 19 Issue: 1 Pages: 5-5

    • DOI

      10.1186/s12902-018-0326-3

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation2018

    • Author(s)
      Izumi T, Imai J, Yamamoto J, Kawana Y, Endo A, Sugawara H, Kohata M, Asai Y, Takahashi K, Kodama S, Kaneko K, Gao J, Uno K, Sawada S, Kalinichenko VV, Ishigaki Y, Yamada T, Katagiri H.
    • Journal Title

      Nat Commun.

      Volume: 9 Issue: 1 Pages: 5300-5300

    • DOI

      10.1038/s41467-018-07747-0

    • URL

      https://pure.teikyo.jp/en/publications/17e764e4-9686-40fb-84e9-eea24f5c6af2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis2018

    • Author(s)
      Kaneko R, Sawada S, Tokita A, Honkura R, Tamura N, Kodama S, Izumi T, Takahashi K, Uno K, Imai J, Yamada T, Miyachi Y, Hasegawa H, Kanai H, Ishigaki Y, Katagiri H
    • Journal Title

      Diabetes Research and Clinical Practice

      Volume: 139 Pages: 43

    • DOI

      10.1016/j.diabres.2018.02.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective insulin resistance with differential expressions of IRS-1 and IRS-2 in human NAFLD livers2018

    • Author(s)
      Honma M, Sawada S, Ueno Y, Murakami K, Yamada T, Gao J, Kodama S, Izumi T, Takahashi K, Tsukita S, Uno K, Imai J, Kakazu E, Kondo Y, Mizuno K, Kawagishi N, Shimosegawa T, Katagiri H.
    • Journal Title

      Int J Obes (Lond).

      Volume: 42 Issue: 9 Pages: 1544

    • DOI

      10.1038/s41366-018-0062-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Vagal signal-mediated tissue regeneration and its therapeutic potential in aged animals2019

    • Author(s)
      井泉知仁、今井淳太、片桐秀樹
    • Organizer
      第62回日本糖尿病学会年次学術集会 シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2021-02-19  

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