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Understanding the mechanism of how central action of amino acids suppresses hepatic glucose production

Research Project

Project/Area Number 26282022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Eating habits
Research InstitutionKanazawa University

Principal Investigator

Inoue Hiroshi  金沢大学, 新学術創成研究機構, 教授 (50397832)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywordsアミノ酸 / 糖産生 / 中枢神経 / 迷走神経 / 肝臓 / 食品 / 糖
Outline of Final Research Achievements

We have reported that histidine administration reduced blood glucose levels in mice, by suppressing hepatic glucose production via central histamine action. Although histidine is expected to be a candidate for blood glucose-lowering nutrient, the precise mechanism of how central histidine suppresses hepatic glucose production remains unclear. Here, we found that central action of histidine and histamine decreased hepatic gluconeogenic genes by activating hepatic STAT3 signaling via the vagus nerve. Moreover, we found that the vagus nerve suppressed hepatic IL-6/STAT3 signaling via the α7-nicotinic acetylcholine receptors, and that central insulin action activated hepatic IL-6/STAT3 signaling by suppressing vagal activity.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (26 results)

All 2017 2016 2015 2014 Other

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 4 results) Presentation (9 results) (of which Invited: 6 results) Book (1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.2017

    • Author(s)
      Watanabe H, Inaba Y, Kimura K, Asahara SI, Kido Y, Matsumoto M, Motoyama T, Tachibana N, Kaneko S, Kohno M, Inoue H*.
    • Journal Title

      J Nutr.

      Volume: 147 Issue: 1 Pages: 52-60

    • DOI

      10.3945/jn.116.231662

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch.2016

    • Author(s)
      Sakai M, Tujimura-Hayakawa T, Yagi T, Yano H, Mitsushima M, Unoki-Kubota H, Kaburagi Y, Inoue H, Kido Y, Kasuga M, Matsumoto M.
    • Journal Title

      Nat Commun.

      Volume: 7 Issue: 1 Pages: 13147-13147

    • DOI

      10.1038/ncomms13147

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia.2016

    • Author(s)
      Morimoto M, Lee EY, Zhang X, Inaba Y, Inoue H, Ogawa M, Shirasawa T, Yokosuka O, Miki T
    • Journal Title

      Nutr Diabetes

      Volume: 27 Issue: 6 Pages: e213-e213

    • DOI

      10.1038/nutd.2016.21

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Centra insulin-action activates Kupffer cells by suppressing hepatic vagal activation through nicotinic alpha 7 acetylcholine receptor.2016

    • Author(s)
      Kimura K, Tanida M, Nagata N, Inaba Y, Watanabe H, Nagashimada M, Ota T, Asahara S, Kido Y, Matsumoto M, Toshinai K, Nakazato M, Shibamoto T, Kaneko S, Kasuga M, Inoue H
    • Journal Title

      Cell reports

      Volume: 14 Issue: 10 Pages: 2362-2374

    • DOI

      10.1016/j.celrep.2016.02.032

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatocyte β-Klotho regulates lipid homeostasis but not body weight in mice.2016

    • Author(s)
      Kobayashi K, Tanaka T, Okada S, Morimoto Y, Matsumura S, Manio MC, Inoue K, Kimura K, Yagi T, Saito Y, Fushiki T, Inoue H, Matsumoto M, Nabeshima Y.
    • Journal Title

      FASEB J.

      Volume: 30 Issue: 2 Pages: 849-62

    • DOI

      10.1096/fj.15-274449

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β cell mass via epigenetic modification of Cdkn1c.2015

    • Author(s)
      Asahara S, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, Kawada Y, Bartolome A, Hashimoto N, Matsuda T, Koyanagi-Kimura M, Kanno A, Hirota Y, Hosooka T, Nagashima K, Nishimura W, Inoue H, Matsumoto M, Higgins MJ, Yasuda K, Inagaki N, Seino S, Kasuga M, Kido Y.
    • Journal Title

      Proceedings of the National Acaddemy of Scienceof the United States of America

      Volume: 112(27) Issue: 27 Pages: 8332-8337

    • DOI

      10.1073/pnas.1422104112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gadd34 regulates liver regeneration in hepatic steatosis.2015

    • Author(s)
      Inaba Y, Furutani T, Kimura K, Watanabe H, Haga S, Kido Y, Yamamoto Y, Harada K, Kaneko S, Oyadomari S, Ozaki M, Kasuga M, Inoue H.
    • Journal Title

      Hepatology

      Volume: 61(4) Issue: 4 Pages: 1343-1356

    • DOI

      10.1002/hep.27619

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice.2015

    • Author(s)
      Tsuneki H, Tokai E, Nakamura Y, Takahashi K, Fujita M, Asaoka T, Kon K, Anzawa Y, Wada T, Takasaki I, Kimura K, Inoue H, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Diabetes

      Volume: 64 Issue: 2 Pages: 459-470

    • DOI

      10.2337/db14-0695

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular basis of brain-mediated regulation of hepatic glucose metabolism.2014

    • Author(s)
      Inoue H.
    • Journal Title

      Diabetol Int.

      Volume: 5 Issue: 3 Pages: 158-164

    • DOI

      10.1007/s13340-014-0185-8

    • NAID

      40020204115

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] p62/SQSTM1 Plays a Protective Role in Oxidative Injury of Steatotic Liver in a Mouse Hepatectomy Model.2014

    • Author(s)
      Haga S, Ozawa T, Yamada Y, Morita N, Nagashima I, Inoue H, Inaba Y, Noda N, Abe R, Umezawa K, Ozaki M.
    • Journal Title

      Antioxid Redox Signal.

      Volume: 21 Issue: 18 Pages: 2515-2530

    • DOI

      10.1089/ars.2013.5391

    • NAID

      120005677747

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis.2014

    • Author(s)
      Tanaka M, Ikeda K, Suganami T, et al.
    • Journal Title

      Nat Commun

      Volume: 5 Issue: 1 Pages: 4982-4982

    • DOI

      10.1038/ncomms5982

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis.2014

    • Author(s)
      Harada K, Kakuda Y, Sato Y, Ikeda H, Shimoda S, Yamamoto Y, Inoue H, Ohta H, Kasashima S, Kawashima A, Nakanuma Y.
    • Journal Title

      J Clin Pathol

      Volume: 67(5) Issue: 5 Pages: 396-402

    • DOI

      10.1136/jclinpath-2013-201815

    • NAID

      120005469783

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 中枢神経性肝糖産生調節における迷走神経の役割2016

    • Author(s)
      井上啓
    • Organizer
      第37回日本肥満学会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 中枢神経による肝糖代謝調節とその破綻2016

    • Author(s)
      井上啓
    • Organizer
      第26回日本病態生理学会
    • Place of Presentation
      金沢
    • Year and Date
      2016-08-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 視床下部を介した栄養素による肝糖代謝調節2015

    • Author(s)
      井上啓
    • Organizer
      第38回日本分子生物学会 第88回日本生化学会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 中枢神経・肝臓クロストークと肥満症におけるその破綻の解明2015

    • Author(s)
      井上啓
    • Organizer
      第36回日本肥満学会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 迷走神経による肝糖産生制御2015

    • Author(s)
      井上啓
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 中枢神経インスリン作用による肝糖代謝調節メカニズムの解明2015

    • Author(s)
      井上啓
    • Organizer
      第88回日本内分泌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 中枢神経による肝臓糖産生の制御2015

    • Author(s)
      井上啓
    • Organizer
      日本薬学会 第135年会
    • Place of Presentation
      神戸学院大学(兵庫県・神戸市)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 視床下部のメタボリックセンサーによる肝臓糖代謝制御2014

    • Author(s)
      井上啓
    • Organizer
      日本栄養・食糧学会第94回関東支部大会
    • Place of Presentation
      東京農業大学(東京都)
    • Year and Date
      2014-11-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 中枢神経による肝糖産生の制御2014

    • Author(s)
      井上啓
    • Organizer
      第19回アディポサイエンス・シンポジウム
    • Place of Presentation
      大阪千里ライフサイエンスセンター(大阪府・豊中市)
    • Year and Date
      2014-08-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] 実験医学「予防医学の扉を開く 食品に秘められたサイエンス-栄養の視床下部での感知と糖代謝への作用-」2017

    • Author(s)
      井上啓
    • Total Pages
      660
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Remarks] 金沢大学新学術創成研究機構革新的統合バイオ研究コア栄養・代謝研究ユニットホームページ

    • URL

      http://inoue.w3.kanazawa-u.ac.jp/about.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] http://inoue.w3.kanazawa-u.ac.jp/index.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 金沢大学脳・肝インターフェースメディシン研究センター井上研究室業績一覧

    • URL

      http://inoue.w3.kanazawa-u.ac.jp/achievement.html

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 肝臓脂肪蓄積抑制剤2015

    • Inventor(s)
      井上啓
    • Industrial Property Rights Holder
      国立大学法人金沢大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-04-23
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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