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Physiological significance of thermosensitive TRPM2 channel

Research Project

Project/Area Number 19209006
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNational Institutes of Natural Sciences Okazaki Research Facilities

Principal Investigator

TOMINAGA Makoto  National Institutes of Natural Sciences Okazaki Research Facilities, 岡崎統合バイオサイエンスセンター, 教授 (90260041)

Co-Investigator(Kenkyū-buntansha) INADA Hitoshi  大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 特任助教 (60419893)
Project Period (FY) 2007 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥49,400,000 (Direct Cost: ¥38,000,000、Indirect Cost: ¥11,400,000)
Fiscal Year 2010: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2009: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2008: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2007: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
KeywordsTRPM2チャネル / 免疫機能 / インスリン分泌 / 膵臓 / 神経科学 / 生理学 / 温度
Research Abstract

Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca^<2+>-permeable cation channel, and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. 1) Upon screening of the compounds, it was clarified that 2-aminoethoxydiphenyl borate (2-APB) exhibited the rapid and reversible inhibition of TRPM2 channels and that 2-APB inhibited heat-evoked insulin release from the pancreatic islets. 2) To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knock-out (TRPM2-KO) mice, and found that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins, suggesting that TRPM2 may be a new target for diabetes therapy. 3) To determine the effects of a small reduction in ambient temperature on energy metabolism, we compared two groups of mice ; one exposed to a cool environment (20℃) and the other maintained in a near-thermoneutral environment (25℃) for 10 days. We found that a small reduction in ambient temperature can affect glucose homeostasis through regulation of insulin secretion and preferentially enhances fat storage in IWAT.

Report

(6 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report   Self-evaluation Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (40 results)

All 2011 2010 2009 2008 2007 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (18 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice.2011

    • Author(s)
      Uchida K, Dezaki K, Damdindorj B, Inada H, Shiuchi T, Mori Y, Yada T, Minokoshi Y, Tominaga M.
    • Journal Title

      Diabetes 60

      Pages: 119-126

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice.2011

    • Author(s)
      Uchida K, Dezaki K, Damdindorj B, Inada H, Shiuchi T, Mori Y, Yada T, Minokoshi Y, Tominaga M.
    • Journal Title

      Diabetes

      Volume: 60 Pages: 119-126

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic adaptation of mice in a cool environment.2010

    • Author(s)
      Uchida K, Shiuchi T, Inada H, Minokoshi Y, Tominaga M.
    • Journal Title

      Pfluger Archiv.Eur.J.Physiol. 459

      Pages: 765-774

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic adaptation of mice in a cool environment2010

    • Author(s)
      Uchida K, Shiuchi T, Inada H, Minokoshi Y, Tominaga M.
    • Journal Title

      Pfluger Archiv. Eur. J. Physiol 459

      Pages: 765-774

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] A 3.5-nm structure of rat TRPV4 cation channel revealed by zernike phase-contrast cryo-EM.2010

    • Author(s)
      Shigematsu H, Sokabe T, Danev R, Tominaga M, Nagayama K.
    • Journal Title

      J.Biol.Chem. 285

      Pages: 4601-4612

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Metabolic adaptation of mice in a cool environment2010

    • Author(s)
      Uchida K., Shiuchi T., Inada H., Minokoshi Y., Tominaga M
    • Journal Title

      Pfluger Archiv.Eur.J.Physiol. 459

      Pages: 765-774

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A 3.5-nm structure of rat TRPV4 cation channel revealed by zernike phase-contrast cryo-EM2010

    • Author(s)
      Shigematsu H., Sokabe T., Danev R., Tominaga M, Nagayama K
    • Journal Title

      J.Biol.Chem. 285

      Pages: 4601-4612

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DIP/WISH-Deficient Mice Reveal Dia- and N-WASP-interacting Protein (DIP/WISH) as a regulator of cytoskeletal dynamics in embryonic fibroblasts2009

    • Author(s)
      Fukumi-Tominaga T, Mori Y, Matsuura A, Kaneko K, Matsui M, Ogata M, Tominaga M.
    • Journal Title

      Genes to Cells 14

      Pages: 4601-4612

    • Related Report
      2009 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] DIP/WISH-Deficient Mice Reveal Dia- and N-WASP-interacting Protein(DIP/WISH)as a regulator of cytoskeletal dynamics in embryonic fibroblasts2009

    • Author(s)
      Fukumi-Tominaga T., Mori Y., Matsuura A., Kaneko K., Matsui M., Ogata M, Tominaga M
    • Journal Title

      Genes to Cells 14

      Pages: 1197-1207

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of TRPM2 channels by 2-APB.2008

    • Author(s)
      Togashi K, Inada H,Tominaga M.
    • Journal Title

      Br.J.Pharm. 153(6)

      Pages: 1324-1330

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of TRPV1 to the bradykinin-evoked nociceptive behavior and excitation of cutaneous sensory neurons2008

    • Author(s)
      Katanosaka K, Banik RK, Giron R, Higashi T, Tominaga M, Mizumura K.
    • Journal Title

      Neurosci. Res. 62

      Pages: 168-175

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular alkalization causes pain sensation through activation of TRPA1.2008

    • Author(s)
      Fujita F, Uchida K, Moriyama T, Shima A, Shibasaki K, Inada H, Sokabe T, Tominaga M.
    • Journal Title

      J. Clon. Invest 118

      Pages: 4049-4057

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of TRPM2 channels by 2-APB2008

    • Author(s)
      Togashi K, Inada H, Tominaga M.
    • Journal Title

      Br.J.Pharmacol 153-(6)

      Pages: 1324-1330

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methyl p-hydroxybenzoate (methyl paraben) causes pain sensation through TRPA1 activation2007

    • Author(s)
      Fujita F, Moriyama T, Higashi T, Shima A and Tominaga M.
    • Journal Title

      Br.J.Pharmacol 151

      Pages: 134-141

    • NAID

      130005448854

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potentiation of TRPA1 activity by PAR-2 through PLC/PIP_2-dependent mechanisms contributes to inflammatory pain2007

    • Author(s)
      Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, Kobayashi K, Obata K, Yamanaka H and Noguchi K.
    • Journal Title

      J.Clin.Invest 117-(7)

      Pages: 1979-1987

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SOI基盤を用いたプレーナー型パッチクランプバイオセンサーの製作2007

    • Author(s)
      浅野 豪文、張 振龍、宇野 秀隆、手老 龍吾、鈴井 光一、中尾 聡、皆藤 孝、柴崎 貢志、富永 真琴、内海 裕一、宇理須 恒雄
    • Journal Title

      表面科学 28-(7)

      Pages: 385-390

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AlphKlotho as a regulator of calcium homeostasis2007

    • Author(s)
      Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T and Nabeshima Y.
    • Journal Title

      Science 316-(5831)

      Pages: 1615-1618

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] TRPM2は細胞内Ca2+濃度変化依存的及び非依存的にインスリン分泌を促進する2011

    • Author(s)
      内田邦敏、出崎克也、Boldbaatar Damdindorj、稲田仁、志内哲也、森泰生、矢田俊彦、箕越靖彦、富永真琴
    • Organizer
      第88回日本生理学大会
    • Place of Presentation
      神奈川
    • Year and Date
      2011-03-29
    • Related Report
      2010 Final Research Report
  • [Presentation] TRPM2は細胞内Ca^<2+>濃度変化依存的及び非依存的にインスリン分泌を促進する2011

    • Author(s)
      内田邦敏、出崎克也、Boldbaatar Damdindorj、稲田仁、志内哲也、森泰生、矢田俊彦、箕越靖彦、富永真琴
    • Organizer
      第88回日本生理学大会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2011-03-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] TRPM2 is a key player for insulin secretion.2010

    • Author(s)
      Uchida K, Dezaki K, Damdindorj B, Mori Y, Minokoshi Y, Yada T, Tominaga M.
    • Organizer
      2nd Leuven TRP meeting.
    • Place of Presentation
      ベルギー
    • Year and Date
      2010-09-23
    • Related Report
      2010 Final Research Report
  • [Presentation] TRPM2 is a key player for insulin secretion2010

    • Author(s)
      Uchida K, Dezaki K, Damdindorj B, Mori Y, Minokoshi Y, Yada T, Tominaga M
    • Organizer
      2^<nd> Leuven TRP meeting
    • Place of Presentation
      リューベン大学、ベルギー
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] TRPM2とインスリン分泌2010

    • Author(s)
      内田邦敏、出崎克也、Boldbaatar Damdindorj、森泰生、箕越靖彦、矢田俊彦、富永真琴
    • Organizer
      第87回日本生理学大会
    • Place of Presentation
      岩手
    • Year and Date
      2010-05-21
    • Related Report
      2010 Final Research Report
  • [Presentation] TRPM2とインスリン分泌2010

    • Author(s)
      内田邦敏、出崎克也、Boldbaatar Damdindorj、森泰生、箕越靖彦、矢田俊彦、富永真琴
    • Organizer
      第87回日本生理学大会
    • Place of Presentation
      岩手県民情報交流センター(岩手)
    • Year and Date
      2010-05-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 寒冷暴露に備えた冷涼環境下での代謝調節2009

    • Author(s)
      内田邦敏、志内哲也、稲田仁、箕越靖彦、富永真琴
    • Organizer
      第56回中部日本生理学会
    • Place of Presentation
      石川
    • Year and Date
      2009-12-04
    • Related Report
      2010 Final Research Report 2009 Self-evaluation Report
  • [Presentation] 寒冷暴露に備えた冷涼環境下での代謝調節2009

    • Author(s)
      内田邦敏、志内哲也、稲田仁、箕越靖彦、富永真琴
    • Organizer
      第56回中部日本生理学会
    • Place of Presentation
      石川県立音楽堂(石川県)
    • Year and Date
      2009-12-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cool environment induced modulation of glucose homeostasis in mice.2009

    • Author(s)
      内田邦敏, 稲田仁, 志内哲也, 箕越靖彦, 富永真琴
    • Organizer
      第36回国際生理学会世界大会
    • Place of Presentation
      京都
    • Year and Date
      2009-07-30
    • Related Report
      2010 Final Research Report
  • [Presentation] Cool environment induced modulation of glucose homeostasis in mice2009

    • Author(s)
      Uchida K, Inada H, Shiuchi T, Minokoshi Y, Tominaga M.
    • Organizer
      第36回国際生理学会世界大会
    • Place of Presentation
      京都
    • Year and Date
      2009-07-30
    • Related Report
      2009 Self-evaluation Report
  • [Presentation] Cool environment induced modulation of glucose homeostasis in mice2009

    • Author(s)
      内田邦敏, 稲田仁, 志内哲也, 箕越靖彦, 富永真琴
    • Organizer
      第36回国際生理学会世界大会
    • Place of Presentation
      京都国際会議場(京都府)
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] 侵害刺激受容に関わるTRPV1およびTRPA1の活性化、制御メカニズム2009

    • Author(s)
      富永真琴
    • Organizer
      日本薬理学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] アルカリpHはTRPA1の活性化を介して痛みを引き起こす2008

    • Author(s)
      内田邦敏, 藤田郁尚, 森山朋子, 島麻子, 柴崎貢志, 稲田仁, 曽我部隆彰
    • Organizer
      第54回中部日本生理学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Intracellular alkalization causes pain sensation through activation of TRPA12008

    • Author(s)
      Fujita F, Uchida K, Moriyama T, Shima A, Shibasaki K, Inada H, Sokabe T, Tominaga M.
    • Organizer
      12th World Cogress on Pain
    • Place of Presentation
      Glasgow, UK
    • Year and Date
      2008-08-08
    • Related Report
      2008 Annual Research Report
  • [Presentation] アルカリpHはTRPA1の活性化を介して痛みを引き起こす2008

    • Author(s)
      富永真琴
    • Organizer
      第30回日本疼痛学会
    • Place of Presentation
      福岡
    • Year and Date
      2008-07-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 2-APBによるTRPM2チャネルの阻害効果の検討2007

    • Author(s)
      稲田 仁、冨樫 和也、富永 真琴
    • Organizer
      第54回中部日本生理学会・第100回近畿生理学談話会合同大会
    • Place of Presentation
      津
    • Year and Date
      2007-10-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] メチルパラベンはTRPA1の活性化を介して痛み感覚を引き起こす2007

    • Author(s)
      曽我部 隆彰、藤田 郁尚、森山 朋子、東 智広、島 麻子、富永 真琴
    • Organizer
      第54回中部日本生理学会・第100回近畿生理学談話会合同大会
    • Place of Presentation
      津
    • Year and Date
      2007-10-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] Physiological significance of the thermosensitive TRP channels2007

    • Author(s)
      Tominaga M
    • Organizer
      2007 Keystone Symposium, The Transient Receptor Potential Ion Channel Super Family
    • Place of Presentation
      Colorado, USA
    • Related Report
      2007 Annual Research Report
  • [Book] Transient Receptor Potential(TRP) Cannels. In"Handbook of Experimental Pharmacology Vol.179"springer2007

    • Author(s)
      Makoto Tominaga
    • Publisher
      springer
    • Related Report
      2010 Final Research Report
  • [Book] ransient Receptor Potential (TRP) Cannels.In"Handbook of Experimental Pahramacology Vol.179"2007

    • Author(s)
      Makoto Tominaga
    • Total Pages
      615
    • Publisher
      Springer
    • Related Report
      2007 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.nips.ac.jp/cs/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.nips.ac.jp/cs/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.nips.ac.jp/cs/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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