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Role of histidine in glucose metabolism

Research Project

Project/Area Number 23300274
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Eating habits, studies on eating habits
Research InstitutionKanazawa University

Principal Investigator

INOUE Hiroshi  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, 教授 (50397832)

Co-Investigator(Kenkyū-buntansha) HAGA Sanae  北海道大学, 保健科学研究院, 博士研究員 (60706505)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsアミノ酸 / 肝糖脂質代謝 / 食生活 / 糖代謝 / 肝臓 / ヒスチジン / 肝糖産生
Research Abstract

We previously revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses hepatic glucose production. Here, we show that increased plasma histidine caused by protein intake resulted in hepatic STAT3 activation. Intravenous and intracerebroventricular administration of histidine also activated hepatic STAT3 and augmented the suppression of hepatic glucose production by insulin. Inhibition of hepatic glucose production by histidine was blocked by inhibiting histamine H1receptors in the central nervous system. Therefore, histidine activates hepatic STAT3 and suppresses hepatic glucose production via central histamine action. In the central nervous system, the mechanisms of histidine and insulin are independent, but have additive inhibitory effects on hepatic glucose prodcution. This suggests that central histidine-mediated suppressive action on hepatic glucose production is a potential target for the treatment of type 2 diabetes.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (43 results)

All 2013 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (21 results) (of which Invited: 5 results) Remarks (4 results)

  • [Journal Article] Histidine augments the suppression of hepatic glucose production by central insulin action2013

    • Author(s)
      Kimura K, Nakamura Y, Inaba Y, Matsumoto M, Kido Y, Asahara S, Matsuda T, Watanabe H, Maeda A, Inagaki F, Mukai C, Takeda K, Akira S, Ota T, Nakabayashi H, Kaneko S, Kasuga M, Inoue H
    • Journal Title

      Diabetes

      Volume: 62(7) Pages: 2266-77

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR432013

    • Author(s)
      Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, Takahashi T, Miyauchi S, Shioi G, Inoue H, Tsujimoto G
    • Journal Title

      Nat Commun

      Volume: 4 Pages: 1829-1829

    • NAID

      120005244704

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypothalamic ATF3 is involved in regulating glucose and energy metabolism in mice2013

    • Author(s)
      Lee YS, Sasaki T, Kobayashi M, Kikuchi O, Kim HJ, Yokota-Hashimoto H, Shimpuku M, Susanti VY, Ido-Kitamura Y, Kimura K, Inoue H, Tanaka-Okamoto M, Ishizaki H, Miyoshi J, Ohya S, Tanaka Y, Kitajima S, Kitamura T
    • Journal Title

      Diabetologia

      Volume: 56(6) Pages: 1383-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin2013

    • Author(s)
      Asahara S, Shibutani Y, Teruyama K, Inoue HY, Kawada Y, Etoh H, Matsuda T, Kimura-Koyanagi M, Hashimoto N, Sakahara M, Fujimoto W, Takahashi H, Ueda S, Hosooka T, Satoh T, Inoue H, Matsumoto M, Aiba A, Kasuga M, Kido Y
    • Journal Title

      Diabetologia

      Volume: 56(5) Pages: 1088-97

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histidine augments the suppression of hepatic glucose production by central insulin action.2013

    • Author(s)
      Kimura K, Nakamura Y, Inaba Y, Matsumoto M, Kido Y, Asahara S, Matsuda T, Watanabe H, Maeda A, Inagaki F, Mukai C, Takeda K, Akira S, Ota T, Nakabayashi H, Kaneko S, Kasuga M, Inoue H.
    • Journal Title

      Diabetes

      Volume: 62 Issue: 7 Pages: 2266-77

    • DOI

      10.2337/db12-1701

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43.2013

    • Author(s)
      Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, Takahashi T, Miyauchi S, Shioi G, Inoue H, Tsujimoto G.
    • Journal Title

      Nat Commun.

      Volume: 4 Issue: 1 Pages: 1829-1829

    • DOI

      10.1038/ncomms2852

    • NAID

      120005244704

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypothalamic ATF3 is involved in regulating glucose and energy metabolism in mice.2013

    • Author(s)
      Lee YS, Sasaki T, Kobayashi M, Kikuchi O, Kim HJ, Yokota-Hashimoto H, Shimpuku M, Susanti VY, Ido-Kitamura Y, Kimura K, Inoue H, Tanaka-Okamoto M, Ishizaki H, Miyoshi J, Ohya S, Tanaka Y, Kitajima S, Kitamura T.
    • Journal Title

      Diabetologia

      Volume: 56(6) Issue: 6 Pages: 1383-1393

    • DOI

      10.1007/s00125-013-2879-z

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin2013

    • Author(s)
      Asahara S
    • Journal Title

      Diabetologia

      Volume: なし Issue: 5 Pages: 1088-1097

    • DOI

      10.1007/s00125-013-2849-5

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CCR5 Plays a Critical Role in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Both Macrophage Recruitment and M1/M2 Status2012

    • Author(s)
      Kitade H, Sawamoto K, Nagashimada M, Inoue H, Yamamoto Y, Sai Y, Takamura T, Yamamoto H, Miyamoto KI, Ginsberg HN, Mukaida N, Kaneko S, Ota T
    • Journal Title

      Diabetes

      Volume: 61(7) Pages: 1680-90

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CITED2 links hormonal signaling to PGC-1α acetylation in the regulation of gluconeogenesis2012

    • Author(s)
      Sakai M, Matsumoto M, Tujimura T, Yongheng C, Noguchi T, Inagaki K, Inoue H, Hosooka T, Takazawa K, Kido Y, Yasuda K, Hiramatsu R, Matsuki Y, Kasuga M
    • Journal Title

      Nat Med

      Volume: 18(4) Pages: 612-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic Reticulum Stress Inhibits STAT3-dependent Suppression of Hepatic Gluconeogenesis via Dephosphorylation and Deacetylation2012

    • Author(s)
      Kimura K, Yamada T, Matusmoto M, Kido Y, Hosooka T, Asahara S, Matsuda T, Ota T, Watanabe H, Sai Y, Miyamoto K, Kaneko S, Kasuga M, Inoue H
    • Journal Title

      Diabetes

      Volume: 61(1) Pages: 61-73

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CCR5 Plays a Critical Role in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Both Macrophage Recruitment and M1/M2 Status2012

    • Author(s)
      Kitade H.
    • Journal Title

      Diabetes

      Volume: 61 Pages: 1680-90

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CITED2 links hormonal signaling to PGC-1α acetylation in the regulation of gluconeogenesis2012

    • Author(s)
      Sakai M.
    • Journal Title

      Nature Medicine

      Volume: 18 Pages: 612-7

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic reticulum stress inhibits STAT3-dependent suppression of hepatic gluconeogenesis via dephosphorylation and deacetylation2012

    • Author(s)
      Kimura K, Yamada T, Matsumoto M, Kasuga M, Inoue H., 他9名
    • Journal Title

      Diabetes

      Volume: 61 Issue: 1 Pages: 61-73

    • DOI

      10.2337/db10-1684

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of TSC2 enhances insulin secretion by increasing the number of mitochondria through activation of mTORC12012

    • Author(s)
      Koyanagi M, et al
    • Journal Title

      PLoS One

      Volume: 6 Issue: 8 Pages: e23238-e23238

    • DOI

      10.1371/journal.pone.0023238

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of glucose metabolism by central insulin action2011

    • Author(s)
      Inoue H
    • Journal Title

      Biomedical Reviews

      Volume: 22 Pages: 31-39

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of TSC2 Enhances Insulin Secretion by Increasing the Number of Mitochondria through Activation of mTORC12011

    • Author(s)
      Koyanagi M, Asahara S, Matsuda T, Hashimoto N, Shigeyama Y, Shibutani Y, Kanno A, Fuchita M, Mikami T, Hosooka T, Inoue H, Matsumoto M, Koike M, Uchiyama Y, Noda T, Seino S, Kasuga M, Kido Y
    • Journal Title

      PLoS One

      Volume: 6(8)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] REGULATION OF GLUCOSE METABOLISM BY CENTRAL INSULIN ACTION2011

    • Author(s)
      Inoue, H.
    • Journal Title

      Biomedical Reviews

      Volume: 22 Pages: 31-39

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 金沢大学次世代重点研究プログラム2013

    • Author(s)
      井上啓
    • Organizer
      第4回「食」による生活習慣病予防医学の展開シンポジウム「食と肝糖産生の制御」
    • Place of Presentation
      金沢
    • Year and Date
      2013-11-21
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは, 中枢神経を介してインスリン作用による肝糖産生抑制を増強する2013

    • Author(s)
      木村久美, 松本道宏, 春日雅人, 井上啓
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Year and Date
      2013-10-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは中枢神経を介してインスリン作用による肝糖新生を抑制する2013

    • Author(s)
      木村久美, 松本道宏, 春日雅人, 井上啓
    • Organizer
      第31回内分泌代謝学サマーセミナー
    • Place of Presentation
      大分
    • Year and Date
      2013-07-12
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] ヒスチジンは, 中枢神経を介してインスリン作用による肝糖産生抑制を増強する2013

    • Author(s)
      木村久美, 井上啓
    • Organizer
      第67回日本栄養・食糧学会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは, 中枢神経を介してインスリン作用による肝糖産生抑制を増強する2013

    • Author(s)
      木村久美, 松本道宏, 春日雅人, 井上啓
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Year and Date
      2013-05-18
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは, 中枢神経を介してインスリン作用による肝糖産生抑制を増強する2013

    • Author(s)
      木村久美, 松本道宏, 春日雅人, 井上啓
    • Organizer
      第86回日本内分泌学術総会
    • Place of Presentation
      仙台
    • Year and Date
      2013-04-25
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは、中枢神経を介してインスリン作用による肝糖産生抑制を増強する2013

    • Author(s)
      木村久美、松本道宏、春日雅人、井上啓
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ヒスチジンは、中枢神経を介してインスリン作用による肝糖産生抑制を増強する2013

    • Author(s)
      木村久美、井上啓
    • Organizer
      第67回日本栄養・食糧学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ヒスチジンは, 中枢神経を介してインスリン作用による肝糖産生抑制を増強する2012

    • Author(s)
      木村久美, 中村雄介, 松本道宏, 春日雅人, 井上啓
    • Organizer
      第24回分子糖尿病学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-12-08
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンによる肝糖代謝調節2012

    • Author(s)
      井上啓
    • Organizer
      第3回「食」による生活習慣病予防医学の展開シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2012-12-06
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは中枢作用を介して肝糖新生を抑制する2012

    • Author(s)
      木村久美, 井上啓
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      京都
    • Year and Date
      2012-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジン摂取による肝糖新生抑制作用の解明2012

    • Author(s)
      木村久美, 太田嗣人, 井上啓
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2012-05-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 小胞体ストレス依存性の STAT3 活性化障害は PERK/eIF2αを介する2012

    • Author(s)
      稲葉有香, 井上啓
    • Organizer
      内分泌代謝学サマーセミナー 30th JES Summer Seminar on Endocrinology & Metabolism
    • Place of Presentation
      群馬
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒスチジンは中枢作用を介して肝糖新生を抑制する2012

    • Author(s)
      木村 久美
    • Organizer
      第33回日本肥満学会
    • Place of Presentation
      ホテルグランヴィア京都(京都府)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒスチジン摂取による肝糖新生抑制作用の解明2012

    • Author(s)
      木村 久美
    • Organizer
      第55回日本糖尿病学会年次学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒスチジンによる肝糖代謝抑制作用の解明2012

    • Author(s)
      木村 久美
    • Organizer
      第30回内分泌代謝学サマーセミナー
    • Place of Presentation
      コンベンションホール麗峰(群馬県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 脳による肝臓エネルギー代謝調節機構2011

    • Author(s)
      井上啓
    • Organizer
      第39回日本肝臓学会西部会
    • Place of Presentation
      岡山コンベンションセンター(招待講演)
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] 食と肝糖産生の制御

    • Author(s)
      井上啓
    • Organizer
      第4回「食」による生活習慣病予防医学の展開シンポジウム
    • Place of Presentation
      金沢
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Histidine decreases hepatic glucose production via the brain action

    • Author(s)
      井上 啓
    • Organizer
      第9回インスリン抵抗性とメタボリックシンドローム研究会
    • Place of Presentation
      ハイアットリージェンシー東京(東京都)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ヒスチジンによる肝糖代謝調節

    • Author(s)
      井上 啓
    • Organizer
      第3回「食」による生活習慣病予防医学の展開シンポジウム
    • Place of Presentation
      KKRホテル金沢(石川県)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] ヒスチジンは、中枢神経を介してインスリン作用による肝糖産生抑制を増強する

    • Author(s)
      木村 久美
    • Organizer
      第24回分子糖尿病学シンポジウム
    • Place of Presentation
      品川インターシティー(東京都)
    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final 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生体統御学部門代謝生理学

    • URL

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

    • Related Report
      2013 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
      2012 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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