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Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance

Research Project

Project/Area Number 15K08427
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionKochi University

Principal Investigator

Kurabayashi Atsushi  高知大学, 教育研究部医療学系連携医学部門, 准教授 (40346713)

Co-Investigator(Kenkyū-buntansha) 柿沼 由彦  日本医科大学, 大学院医学研究科, 大学院教授 (40233944)
井上 啓史  高知大学, 教育研究部医療学系臨床医学部門, 教授 (00294827)
Co-Investigator(Renkei-kenkyūsha) FURIHATA MUTSUO  高知大学, 教育研究部医療学系連携医学部門, 教授 (10209158)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords虚血再灌流モデル / 糖取り込み / 糖新生 / 副交感神経 / 迷走神経 / 末梢虚血再刊流刺激 / 糖代謝 / 副交感神経系 / 肝臓 / 血糖低下 / 臓器保護性
Outline of Final Research Achievements

Our previous study revealed that hindlimb ischaemia-reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. Using C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity and hepatic gluconeogenic enzyme activities were assessed. IR decreased BS levels and leaded to neuronal activation of the center of the PNS. IR specifically downregulated hepatic gluconeogenic enzyme expression and activities and accelerated hepatic glucose uptake. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism.

Report

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

    (4 results)

All 2018 2017 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance2018

    • Author(s)
      Kurabayashi Atsushi、Tanaka Chiharu、Matsumoto Waka、Naganuma Seiji、Furihata Mutsuo、Inoue Keiji、Kakinuma Yoshihiko
    • Journal Title

      Diabetes Research and Clinical Practice

      Volume: 139 Pages: 288-299

    • DOI

      10.1016/j.diabres.2018.03.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 後肢虚血―再灌流刺激の肝糖代謝への影響と中枢神経を介したそのメカニズム2017

    • Author(s)
      倉林 睦, 田中千遥, 松本和花, 長沼誠二, 降幡睦夫,柿沼由彦
    • Organizer
      日本糖尿病学会年次学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Hindlimb IR effect on glucose metabolism in the hepatocytes via a brain-liver neurocircuit2017

    • Author(s)
      倉林 睦, 田中千遥, 松本和花, 長沼誠二, 降幡睦夫
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 後肢虚血ー再還流モデルにおける糖代謝への影響2015

    • Author(s)
      倉林 睦、黒江 崇史、降幡 睦夫
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場 (名古屋市)
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report

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

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