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Significance of homeodynamic regulation by hypothalamic orexin in preventing obesity and type 2 diabetes

Research Project

Project/Area Number 15K09380
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionUniversity of Toyama

Principal Investigator

TSUNEKI Hiroshi  富山大学, 大学院医学薬学研究部(薬学), 准教授 (20332661)

Co-Investigator(Kenkyū-buntansha) 笹岡 利安  富山大学, 大学院医学薬学研究部(薬学), 教授 (00272906)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病 / エネルギー・糖質代謝異常 / 生物時計 / インスリン抵抗性 / エネルギー・糖脂質代謝異常 / 脳・神経 / 生体リズム / オレキシン / 睡眠
Outline of Final Research Achievements

Brain plays a major role in maintenance of energy homeostasis by coordinating daily rhythms in biological clock, sleep/wake, and metabolism. To reveal the mechanism, the present study investigated the functional significance of hypothalamic orexin system. In obese mice, amplification of the daily action of orexin by using orexin agonist in awake period or orexin antagonist in resting period improved glucose metabolism, whereas orexin deficiency caused severe obesity and metabolic abnormalities in the adipose tissue and the liver. Furthermore, orexin and estrogen synergistically prevented obesity-associated metabolic disorders. Thus, homeodynamic regulation of glucose and energy metabolism by hypothalamic orexin system appears to be a key factor for preventing metabolic disorders, including obesity and type 2 diabetes.

Report

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

    (37 results)

All 2018 2017 2016 2015 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (24 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Book (5 results) Remarks (3 results)

  • [Journal Article] Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders2018

    • Author(s)
      Tsuneki H, Wada T, Sasaoka T.
    • Journal Title

      Pharmacol Ther

      Volume: 印刷中 Pages: 25-44

    • DOI

      10.1016/j.pharmthera.2017.12.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice.2016

    • Author(s)
      Tsuneki H, Kon K, Ito H, Yamazaki M, Takahara S, Toyooka N, Ishii Y, Sasahara M, Wada T, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Endocrinology.

      Volume: 157 Issue: 11 Pages: 4146-4157

    • DOI

      10.1210/en.2016-1404

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sleep Control, GPCRs, and Glucose Metabolism.2016

    • Author(s)
      Tsuneki H, Sasaoka T, Sakurai T.
    • Journal Title

      Trends Endocrinol Metab.

      Volume: 27(9) Issue: 9 Pages: 633-42

    • DOI

      10.1016/j.tem.2016.06.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nighttime administration of nicotine improves hepatic glucose metabolism via the hypothalamic orexin system in mice.2016

    • Author(s)
      Tsuneki H, Nagata T, Fujita M, Kon K, Wu N, Takatsuki M, Yamaguchi K, Wada T, Nishijo H, Yanagisawa M, Sakurai T, Sasaoka T.
    • Journal Title

      Endocrinology

      Volume: 157 Issue: 1 Pages: 195-206

    • DOI

      10.1210/en.2015-1488

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Orexin regulates glucose homeodynamics with daily rhythm.2015

    • Author(s)
      Tsuneki H, Wada T, Sasaoka T
    • Journal Title

      Orexin and Sleep. Springer International Publishing Switzerland

      Volume: 2015 Pages: 381-394

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 睡眠と糖代謝の連係調節における視床下部オレキシンの役割2018

    • Author(s)
      恒枝宏史、今 寛太、和田 努、笹岡利安
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Timed administration of orexin receptor modulators improved glucose metabolism in type 2 diabetic mice2017

    • Author(s)
      Tsuneki H, Wada T, Sasaoka T.
    • Organizer
      13th International Symposium on Insulin Receptor and Insulin Action
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hypothalamic orexin and estrogen synergistically improved glucose metabolism in diet-induced obese mice2017

    • Author(s)
      Kon K, Tsuneki H, Takata S, Koshida C, Wada T, Sasaoka T
    • Organizer
      The 16th Japan-Korea Diabetic Nephropathy Seminar
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 肥満マウスにおいて視床下部オレキシン系は白色脂肪組織の慢性炎症を防止する2017

    • Author(s)
      今 寛太,恒枝宏史,越田千晶,東海絵美,和田 努,笹岡利安
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 嗅覚系を起点とした視床下部オレキシン系を介する中枢性糖代謝調節機構の解析2017

    • Author(s)
      恒枝宏史,大西兼悟,松岡幸奈,和田 努,笹岡利安
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病における不眠の病態と対策2017

    • Author(s)
      笹岡利安
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オレキシンによる睡眠・覚醒と糖代謝調節2017

    • Author(s)
      笹岡利安
    • Organizer
      第39回日本臨床栄養学会総会 第38回日本臨床栄養協会総会 第15回大連合大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 嗅覚の刺激および破壊がマウスの糖代謝に及ぼす影響の解析2017

    • Author(s)
      大西兼悟,恒枝宏史,松岡幸奈,松田大樹,和田 努,笹岡利安
    • Organizer
      日本薬学会北陸支部第129回例会
    • Related Report
      2017 Annual Research Report
  • [Presentation] エストロゲンによる糖・エネルギー代謝調節における視床下部オレキシン系の役割2017

    • Author(s)
      今 寛太,恒枝宏史,髙田慎治郎,越田千晶,大西兼悟,小野木康弘,石川明香里,渡邊愛理,王生美沙,長谷川 颯,松澤崇俊,和田 努,笹岡利安
    • Organizer
      第29回分子糖尿病学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dual orexin receptor antagonist ameliorates impaired sleep/wake cycle and glucose metabolism in diabetic db/db mice in a treatment-time dependent manner.2016

    • Author(s)
      Kon K, Tsuneki H, Wada T, Sasaoka T.
    • Organizer
      The 15th Japan-Korea Diabetic Nephropathy Seminar
    • Place of Presentation
      Asahikawa
    • Year and Date
      2016-10-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] The ameliorating effect of suvorexant, a dual orexin receptor antagonist, on glucose metabolism in type 2 diabetic db/db mice.2016

    • Author(s)
      Tsuneki H, Kon K, Wada T, Sasaoka T.
    • Organizer
      52nd EASD Annual Meeting
    • Place of Presentation
      Munich, Germany
    • Year and Date
      2016-09-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 概日リズムに基づいたオレキシン系の活性化による糖代謝異常治療戦略.2016

    • Author(s)
      笹岡利安,恒枝宏史.
    • Organizer
      日本睡眠学会第41回定期学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-07
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 不眠症治療薬スボレキサントによる視床下部オレキシン系を介した糖代謝改善効果.2016

    • Author(s)
      今 寛太,恒枝宏史,和田 努,笹岡利安
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 中枢性糖代謝調節機構におけるドパミンD2受容体系の機能的意義の解析.2016

    • Author(s)
      恒枝宏史,東海絵美,髙月真由美,大西兼悟,今 寛太,和田 努,笹岡利安.
    • Organizer
      第59回日本糖尿病学会年次学術集会
    • Place of Presentation
      京都
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 視床下部オレキシンによる睡眠と糖代謝の連係調節の意義.2016

    • Author(s)
      恒枝宏史、和田 努、笹岡利安.
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 視床下部オレキシンの「動的」血糖制御を標的とした糖尿病治療の新戦略.2016

    • Author(s)
      恒枝宏史、和田 努、笹岡利安.
    • Organizer
      第89回日本薬理学会年会シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] オレキシン受容体拮抗薬による2型糖尿病マウスの睡眠と肝糖代謝の改善効果.2016

    • Author(s)
      恒枝宏史,今 寛太,和田 努,笹岡 利安.
    • Organizer
      第3回肝臓と糖尿病・代謝研究会
    • Place of Presentation
      金沢
    • Related Report
      2016 Research-status Report
  • [Presentation] 雌性オレキシン欠損マウスが高度肥満および脂肪組織の慢性炎症を呈する機序の解析.2016

    • Author(s)
      越田千晶,恒枝宏史,浅岡健広,和田 努,笹岡利安.
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      金沢
    • Related Report
      2016 Research-status Report
  • [Presentation] 視床下部オレキシンによる自律神経系と小胞体ストレス応答を介したマウス肝糖産生の調節機構.2015

    • Author(s)
      笹岡利安,和田 努,恒枝宏史.
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] オレキシン系を標的とした生体リズム制御による2型糖尿病マウスの糖代謝改善効果.2015

    • Author(s)
      今 寛太,恒枝宏史,東海絵美,永田貴嗣,和田 努,笹岡利安.
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Hypothalamic orexin as a chronotherapeutic target for type 2 diabetes.2015

    • Author(s)
      Tsuneki H, Nagata T, Kon K, Wada T, Sasaoka T.
    • Organizer
      American Diabetes Association (ADA) 75th Scientific Sessions
    • Place of Presentation
      Boston, U.S.A.
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 視床下部オレキシンによる加齢および肥満病態での脂肪組織機能の防御効果の解析.2015

    • Author(s)
      東海絵美,恒枝宏史,浅岡健広,今 寛太,髙橋佳佑,越田千晶,布目幸久,和田 努,笹岡利安.
    • 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
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 新規不眠症治療薬スボレキサントの時間治療による2型糖尿病マウスの糖代謝改善効果.2015

    • Author(s)
      今 寛太,恒枝宏史,和田 努,笹岡利安.
    • 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
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] ニコチン作用から見た視床下部オレキシン系の日内リズム調節が高血糖に及ぼすインパクト.2015

    • Author(s)
      恒枝宏史,永田貴嗣,藤田樹生,和田 努,笹岡利安.
    • 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
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Book] オレキシン受容体拮抗薬が糖代謝に及ぼす影響.睡眠医療.2018

    • Author(s)
      笹岡利安,恒枝宏史
    • Total Pages
      8
    • Publisher
      ライフ・サイエンス社
    • Related Report
      2017 Annual Research Report
  • [Book] オレキシンと糖代謝.睡眠医療.2017

    • Author(s)
      笹岡利安,恒枝宏史
    • Total Pages
      8
    • Publisher
      ライフ・サイエンス社
    • ISBN
      9784898015834
    • Related Report
      2017 Annual Research Report
  • [Book] 診断と治療のABC 124.糖尿病合併症.糖尿病と睡眠障害(うつ病を含む).2017

    • Author(s)
      笹岡利安,恒枝宏史
    • Total Pages
      9
    • Publisher
      最新医学社
    • Related Report
      2017 Annual Research Report
  • [Book] オレキシンによる睡眠の制御と代謝機能.睡眠・覚醒制御機構研究の新展開.医学のあゆみ.2017

    • Author(s)
      笹岡利安,恒枝宏史
    • Total Pages
      7
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2017 Annual Research Report
  • [Book] 自律神経系の概日リズムとオレキシン. Annual Review 2016 糖尿病・代謝・内分泌.2016

    • Author(s)
      笹岡利安, 恒枝宏史.
    • Total Pages
      7
    • Publisher
      中外医学社
    • Related Report
      2016 Research-status Report
  • [Remarks] 富山大学 大学院医学薬学研究部(薬学) 病態制御薬理学研究室

    • Related Report
      2017 Annual Research Report
  • [Remarks] 富山大学 大学院医学薬学研究部(薬学) 病態制御薬理学研究室

    • URL

      http://www.pha.u-toyama.ac.jp/clinphar/index-j.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 富山大学 大学院医学薬学研究部(薬学)病態制御薬理学研究室

    • URL

      http://www.pha.u-toyama.ac.jp/clinphar/index-j.html

    • Related Report
      2015 Research-status Report

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

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