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Molecular mechanism for highly sensitive response to peripheral hormones in hypothalamic neurons and homeostatic role

Research Project

Project/Area Number 16K15182
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionJichi Medical University

Principal Investigator

Yada TOSHIHIKO  自治医科大学, 医学部, 教授 (60166527)

Co-Investigator(Renkei-kenkyūsha) MASANORI Nakata  自治医科大学, 医学部, 准教授 (10305120)
TATSUYA Dezaki  自治医科大学, 医学部, 准教授 (90337329)
YUSAKU Iwasaki  自治医科大学, 医学部, 講師 (60528420)
SHIGETOMO Suyama  自治医科大学, 医学部, 助教 (80528414)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsインスリン / 視床下部 / 室傍核 / 神経内分泌 / オキシトシン神経 / PDK1 / PDK1 / 高感受性 / インスリン感受性 / 細胞情報伝達 / 弓状核 / 視交叉上核
Outline of Final Research Achievements

Peripheral injection of insulin induced c-Fos in hypothalamic paraventricular nucleus (PVN) particularly in large-sized oxytocin neurons, and increased plasma oxytocin levels in mice. Very low levels of nsulin at picomolar concentrations increased cytosolic free calcium in single neurons isolated from PVN mostly in large-sized neuroendocrine oxytocin neurons. In oxytocin neuron-specific PDK1 knockdown mice via Cre-LoxP system, picomolar insulin failed to activate neuroendocrine oxytocin neurons and peripheral insulin-induced rises in plasma oxytocin disappeared.
These results indicate that large-sized neuroendocrine oxytocin neurons in PVN respond to very low levels of insulin via mechanisms involving PDK1.

Report

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

    (14 results)

All 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] PDK1-FoxO1 pathway in AgRP neurons of arcuate nucleus promotes bone formation via GHRH-GH-IGF1 axis.2017

    • Author(s)
      Sasanuma H, Nakata M, Kumari P, Nakae J, Yada T
    • Journal Title

      Molecular Metabolism

      Volume: 6(5) Issue: 5 Pages: 428-439

    • DOI

      10.1016/j.molmet.2017.02.003

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glucagon-like peptide-1 and insulin synergistically activate vagal afferent neurons.2017

    • Author(s)
      Iwasaki, Y., Goswami, C., and Yada, T.
    • Journal Title

      Neuropeptide

      Volume: 65 Pages: 77-82

    • DOI

      10.1016/j.npep.2017.05.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous α2A-adrenoceptor-operated sympathoadrenergic tones attenuate insulin secretion via cAMP/TRPM2 signaling.2017

    • Author(s)
      Ito K, Dezaki K, Yoshida M, Yamada H, Miura R, Rita RS, Ookawara S, Tabei K, Kawakami M, Hara K, Morishita Y, Yada T, Kakei M
    • Journal Title

      Diabetes

      Volume: 66(3) Issue: 3 Pages: 699-709

    • DOI

      10.2337/db16-1166

    • NAID

      40021363366

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suprachiasmatic Vasopressin to Paraventricular Oxytocin Neurocircuit in the Hypothalamus Relays Light Reception to Inhibition of Feeding Behavior.2017

    • Author(s)
      Santoso P, Nakata M, Ueta Y, Toshihiko Yada T
    • Journal Title

      Am J Physiol Endocrinol Metab.

      Volume: 印刷中 Issue: 4 Pages: E478-E488

    • DOI

      10.1152/ajpendo.00338.2016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Fibroblast growth factor 21, assisted by elevated glucose, activates paraventricular nucleus NUCB2/Nesfatin-1 neurons to produce satiety under fed states.2017

    • Author(s)
      Santoso P, Nakata M, Shiizaki K, Boyang Z, Parmila K, Otgon-Uul Z, Hashimoto K, Satoh T, Mori M, Kuro-O M, Yada T
    • Journal Title

      Sci Rep

      Volume: 印刷中 Issue: 1 Pages: 45819-45819

    • DOI

      10.1038/srep45819

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.2016

    • Author(s)
      Suyama S, Maekawa F, Maejima Y, Kubota N, Kadowaki T, Yada T
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 30796-30796

    • DOI

      10.1038/srep30796

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 希少糖アルロースによるGLP-1放出、求心性迷走神経を介した摂食・糖代謝制御と肥満症改善.2017

    • Author(s)
      矢田俊彦,岩﨑有作,比良徹,原博,Goswami Chayon,仙度光麻,徳田雅明,出崎克也
    • Organizer
      第122回日本解剖学会総会・全国学術集会(日本解剖学会・日本生理学会合同シンポジウム)
    • Place of Presentation
      長崎大学坂本キャンパス(長崎県長崎市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] 摂食制御の理解から代謝疾患の治療へ2017

    • Author(s)
      矢田俊彦
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(静岡県浜松市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] GLP-1とインスリンは相乗的に求心性迷走神経を活性化させる2017

    • Author(s)
      岩崎有作,矢田俊彦
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 弓状核AgRPニューロンのPDK1シグナルを起点とした血圧調節経路2017

    • Author(s)
      中田正範,中江淳,Parmila Kumari,張博洋,小川渉,矢田俊彦
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] インスリンによる室傍核オキシトシン神経活性化と血中オキシトシン濃度増加2017

    • Author(s)
      張博洋,中田正範,Parmila Kumari,小川渉,矢田俊彦
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] GLP-1とインスリンの協働作用による求心性迷走神経活性化:食後機能、治療効果の推定機序2017

    • Author(s)
      岩崎有作,ごしゃみ ちゃよん,矢田俊彦
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Na+,K+-ATPase in the hypothalamic arcuate nucleus senses lowering glucose to initiate feeding behavior.2016

    • Author(s)
      Yada T, Kurita H, Xu KY, Santoso P, Yang Y, Dezaki K, Nakata M
    • Organizer
      46th annual meeting of The Society for Neuroscience
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 視床下部背内側核GABA作動性ニューロンによる摂食亢進作用.2016

    • Author(s)
      須山成朝,オトゴンウール ゼセミ,小野寺宏,矢田俊彦
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京ファッションタウンビル(東京都江東区)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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