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2007 Fiscal Year Final Research Report Summary

Roles of TRP channels in response to exposure with high concentrations of glucose in pancreatic β cells

Research Project

Project/Area Number 17590224
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionUniversity of Shizuoka

Principal Investigator

ISHIKAWA Tomohisa  University of Shizuoka, Department of Pharmacology, School of Pharmaceutical Sciences, Ph.D. Professor (10201914)

Project Period (FY) 2005 – 2007
KeywordsPharmacology / β-cells / Signal transduction / Hyposmolarity / TRP / Insulin secretion / Hydrogen peroxide / Anontosis
Research Abstract

(1) Cell swelling-induced insulin secretion and TRP channels
In isolated rat pancreatic β-cells, hypotonic stimulation elicited an increase in cytosolic Ca^<2+> concentration ([Ca^<2+>]_i) at 2.8 mM glucose. The hypotonically induced [Ca^<2+>]i elevation was significantly suppressed by Gd^<3+>, amiloride, 2-aminoethoxydiphenyl borate (2-APB), and ruthenium red, all cation channel blockers. Whole-cell patch clamp analysis showed that hypotonic stimulation induced membrane depolarization of β-cells and produced outwardly rectifying cation currents; Gd^<3+> inhibited both responses. Hypotonic stimulation also increased insulin secretion from isolated rat islets, and Gd^<3+> significantly suppressed this secretion. Taken together, these results suggest that osmotic cell swelling activates cation channels, possibly TRP channels, in rat pancreatic β-cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca^<2+> channels, thus elevating insulin secretion.
… More (2) β-Cell apoptosis and TRP channels
Treatment of pancreatic β-cell line INS-1 with 100 μM H_2O_2 for 18 h significantly increased apoptosis cells. The apoptosis was abolished by BAPTA/AM, an intracellular Ca^<2+> chelator, and by 2-APB, which blocks IP_3 receptors and cation channels, but not by nicardipine. Interestingly, the anti-apoptotic effect of BAPTA/AM or 2-APB was not induced when the drug was applied 30 min after the addition of H_2O_2. H_2O_2 also induced [Ca^<2+>]_i elevation which consisted of two phases; the first transient phase and the second gradually developing one. The [Ca^<2+>]I elevation was significantly inhibited by 2-APB. In addition, PP2, a selective inhibitor of Src family, significantly inhibited the H_2O_2-induced apoptosis. These results suggest that [Ca^<2+>]I elevation induced by IP3-mediated Ca^<2+> release and/or Ca^<2+>entry through cation channels plays a pivotal role in H_2O_2-induced β-cell apoptosis, which is mediated by the activation of Src family, and that the first [Ca^<2+>]_i elevation within 30 min after the addition of H_2O_2 seems to be a obligatory step triggering β-cell apoptosis. Less

  • Research Products

    (54 results)

All 2008 2007 2006 2005

All Journal Article (20 results) (of which Peer Reviewed: 9 results) Presentation (34 results)

  • [Journal Article] Dual effect of nitric oxide on ATP-sensitive K^+ channels in rat pancreatic β-cells2008

    • Author(s)
      Takaaki Sunouchi
    • Journal Title

      PfliigersArch.Eur.J.Physiol 456

      Pages: 573-579

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Dual effect of nitric oxide on ATP-sensitive K+ channels in rat pancreatic β-cells2008

    • Author(s)
      Sunouchi T, Suzuki K, Nakayama K, Ishikawa T
    • Journal Title

      Pfltigers Arch-Eur J Physiol 456

      Pages: 573-579

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of α^<2C>-adrenoceptors in local cooling -induced reduction of skin blood flow in mice2007

    • Author(s)
      Masaki Honda
    • Journal Title

      Br.J.Pharmacol 152

      Pages: 91-100

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Role of α_(2c)-adrenoceptors in local cooling-induced reduction of skin blood flow in mice2007

    • Author(s)
      Honda, M, Suzuki, M, Nakayama, K, Ishikawa, T
    • Journal Title

      Br J Pharmacol 152

      Pages: 91-100

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Passive stretching produces Akt-and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice2006

    • Author(s)
      Yoshihiko Ito
    • Journal Title

      PfliigersArch.Eur.J.Physiol 451

      Pages: 803-813

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats2006

    • Author(s)
      Tadachika Koganezawa
    • Journal Title

      Br.J.Pharmacol 148

      Pages: 579-586

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of stretch-activated cation channels in hypotonically inducedinsulin secretion in rat pancreatic β-cells2006

    • Author(s)
      Miki Takii
    • Journal Title

      Am.J.Physiol.Cell Physiol 291

      Pages: 1405-1411

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Arp感受性K^+チャネルを介さないグルコース応答性インスリン分泌機構NOおよび細胞膨張によるインスリン分泌調節を中心に2006

    • Author(s)
      石川 智久
    • Journal Title

      日本薬理学雑誌 128

      Pages: 208-213

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice2006

    • Author(s)
      Ito, Y, Obara, K, Ikeda, R, Ishii, M, Tanabe, Y, Ishikawa, T, Nakayama, K
    • Journal Title

      Pfltigers Arch-Eur J Physiol 451

      Pages: 803-813

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats2006

    • Author(s)
      Koganezawa, T, Ishikawa, T, Fujita, Y, Yamashita, T, Tajima, T, Honda, M, Nakayama, K
    • Journal Title

      Br J Pharmacol 148

      Pages: 579-586

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of stretch-activated cation channels in hypotonically induced insulin secretion in rat pancreatic β-cells2006

    • Author(s)
      Takii, M, Ishikawa, T, Tsuda, H, Kanatani, K, Sunouchi, T, Kaneko, Y, Nakayama, K
    • Journal Title

      Am J Physiol Cell Physiol 291

      Pages: C1405-C1411

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of novel protein kinase C isoforms in carbachol-stimulated insulin secretion from rat pancreatic islets2005

    • Author(s)
      Tomohisa Ishikawa
    • Journal Title

      Life Sci 77

      Pages: 462-469

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Ionic mechanism for contractile response to hyposmotic challenge in caninebasilar arteries2005

    • Author(s)
      Shunsuke Yano
    • Journal Title

      Am.J.Physiol.Cell Physiol 288

      Pages: 702-709

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Interactive role of protein kinase Cδ with Rho-kinase in the development of cerebral vasospasm in a calline two-hemorrhage model2005

    • Author(s)
      Kazuo Obara
    • Journal Title

      J.Vasc.Res 42

      Pages: 67-76

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Facilitation of L-type Ca^<2+> currents by fluid flow in rabbit cerebral artery myocytes2005

    • Author(s)
      Satoshi Amano
    • Journal Title

      J.Phannacol.Sci 98

      Pages: 425-429

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] 脳血管におけるストレッチと低浸透圧刺激に対する筋原性反応のイオンメカニズム2005

    • Author(s)
      石川 智久
    • Journal Title

      日本薬理学雑誌 126

      Pages: 262-266

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of novel protein kinase C isoforms in carbachol-stimulated insulin secretion from rat pancreatic islets2005

    • Author(s)
      Ishikawa, T, Iwasaki, E, Kanatani, K, Sugino, F, Kaneko, Y, Obara, K, Nakayama, K
    • Journal Title

      Life Sci 77

      Pages: 462-469

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ionic mechanism for contractile response to hyposmotic challenge in canine basilar arteries2005

    • Author(s)
      Yano, S, Ishikawa, T, Tsuda, H, Obara, K, Nakayama, K
    • Journal Title

      Am J Physiol Cell Physiol 288

      Pages: C702-C709

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interactive role of protein kinase CS with Rho-kinase in the development of cerebral vasospasm in a canine two-hemorrhage model2005

    • Author(s)
      Obara, K, Nishizawa, S, Koide, M, Nozawa, K, Mitate, A, Ishikawa, T, Nakayama, K
    • Journal Title

      J Vasc Res 42

      Pages: 67-76

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Facilitation of L-type Ca^(2+) currents by fluid flow in rabbit cerebral artery myocytes2005

    • Author(s)
      Amano, S, Ishikawa, T, Nakayama, K
    • Journal Title

      J Pharmacol Sci 98

      Pages: 425-429

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 過酸化水素による膵β細胞アポトーシスにおけるカルシウムの役割2008

    • Author(s)
      高田 正弘
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-03-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ラット膵島初代培養による内皮型NO含成酵素の発現変化2008

    • Author(s)
      加藤 佑一
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 治験・臨床開発を担うスタッフ養成のための薬学系大学院夜間講座-4年目の現況-2008

    • Author(s)
      後藤 貴裕
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-03-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Interactive role of protein kinase Cα and protein phosphatase 2A in the stretch-induced triphospholylation of myosin light chain in canine cerebral artery2008

    • Author(s)
      Kazuo Obara
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-03-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Facilitatory effects of female hormones on cold-induced reduction of skinblood flow in mice2008

    • Author(s)
      Mika Suzuki
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-03-19
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The role of phospholipase A_2 product in U46619-induced contraction medlated by voltage dependent Ca^<2+> channel in the presence of indomethacin2008

    • Author(s)
      Ami Nishijima
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-03-17
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Temporal changes in the contribution of protein kinase C isoforms to myogenic constriction in rat posterior cerebral arteries2007

    • Author(s)
      Kashihara, T, Nakayama, K, Ishikawa, T
    • Organizer
      American Heart Association Scientific Session 2007
    • Place of Presentation
      Florida, U.S.A.
    • Year and Date
      20071104-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Roles of protein kinase C isoforms and Rho-kinase in long-term pressure-induced myogenic constriction in rat posterior cerebral arteries2007

    • Author(s)
      Toshihide Kashihara
    • Organizer
      第5回国際受容体シンポジウム
    • Place of Presentation
      静岡市
    • Year and Date
      20070510-11
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Mechanism for local cooling-induced reduction of skin blood flow in mice2007

    • Author(s)
      Mika Suzuki
    • Organizer
      第5回国際受容体シンポジウム
    • Place of Presentation
      静岡市
    • Year and Date
      20070510-11
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Mechanism for local cooling-induced reduction of skin blood flow in mice2007

    • Author(s)
      Suzuki, M, Honda, M, Nakayama, K, Ishikawa, T
    • Organizer
      5th International Symposium on Receptor Mechanisms, Signal Transduction and Drug Effects
    • Place of Presentation
      Shizuoka, Japan
    • Year and Date
      20070510-11
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Roles of protein kinase C isoforms and Rho-kinase in long-term pressure-induced myogenic constriction in rat posterior cerebral arteries2007

    • Author(s)
      Kashihara, T, Nakayama, K, Ishikawa, T
    • Organizer
      5th International Symposium on Receptor Mechanisms, Signal Transduction and Drug Effects
    • Place of Presentation
      Shizuoka, Japan
    • Year and Date
      20070510-11
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Physiological role of nitric oxide in pancreatic β-cells2007

    • Author(s)
      Tomohisa Ishikawa
    • Organizer
      Pharmacology Seminar at the University of Vermont
    • Place of Presentation
      Vermont,U.S.A.
    • Year and Date
      2007-11-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Temporal changes in the contribution of protein kinase C isoforms to myogenic constriction in rat posterior cerebral arteries2007

    • Author(s)
      Toshihide Kashihara
    • Organizer
      American Heart Association Scientific Session 2007
    • Place of Presentation
      Florida,U.S.A.
    • Year and Date
      2007-11-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 冷却によるラット尾動脈における収縮反応性変化の薬理学的解析2007

    • Author(s)
      齊藤 真也
    • Organizer
      第117回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Year and Date
      2007-10-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 膵β細胞株INS-1細胞のアポトーシスに対する一酸化窒素の二面的な作用2007

    • Author(s)
      野口 亜希子
    • Organizer
      第117回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Year and Date
      2007-10-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ラット後大脳動脈圧誘発性収縮におけるRhoキナーゼとプロテインキナーゼCの役割の相違2007

    • Author(s)
      柏原 俊英
    • Organizer
      第112回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Year and Date
      2007-09-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 新たな創薬ターゲットとしての膵β細胞機能調節因子2007

    • Author(s)
      石川 智久
    • Organizer
      生体機能と創薬シンポジウム2007
    • Place of Presentation
      金沢市
    • Year and Date
      2007-09-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Involvements of Rho-kinase and protein kinase C in strech-induced triphosphorylation of myosin light chain in canine basilar artery2007

    • Author(s)
      Kazuo Obara
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2007-03-15
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Role of protein kinase C isoforms in pressure-induced myogenic constriction in rat posterior cerebral arteries2007

    • Author(s)
      Toshihide Kashihara
    • Organizer
      第80回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2007-03-14
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ラット後大脳動脈における圧誘発性血管収縮反応の細胞内情報伝達機構の時間的変化2006

    • Author(s)
      柏原 俊英
    • Organizer
      第16回日本循環薬理学会
    • Place of Presentation
      東京
    • Year and Date
      2006-12-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] マウス局所性冷却誘発皮膚血流減少反応におけるα_2cアドレナリン受容体の関与2006

    • Author(s)
      本多 正樹
    • Organizer
      第16回日本循環薬理学会
    • Place of Presentation
      東京
    • Year and Date
      2006-12-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 骨格筋の受動的伸展刺激(ストレッチ)による糖取り込みの増加2006

    • Author(s)
      伊藤 由彦
    • Organizer
      第11回静岡健康・長寿学術フォーラム
    • Place of Presentation
      静岡市
    • Year and Date
      2006-10-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] マウス局所性冷却誘発皮膚血流減少反応におけるα_2cアドレナリン受容体の関与2006

    • Author(s)
      本多 正樹
    • Organizer
      第115回日本薬理学会関東部会
    • Place of Presentation
      高崎市
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] インスリン分泌調節に寄与する諸因子の解析-NOを中心に2006

    • Author(s)
      石川 智久
    • Organizer
      第6回Islet Biology研究会
    • Place of Presentation
      東京
    • Year and Date
      2006-07-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 骨格筋の伸展刺激によるAkt,p38MAPKの活性化を伴うGLUT4の膜移行と糖取り込みの増加2006

    • Author(s)
      伊藤 由彦
    • Organizer
      第52回日本薬学会東海支部総会・大会
    • Place of Presentation
      静岡市
    • Year and Date
      2006-07-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] マウスにおける冷却誘発皮膚血流減少反応へのα_2Cアドレナリン受容体の関与2006

    • Author(s)
      鈴木 美香
    • Organizer
      第52回日本薬学会東海支部総会・大会
    • Place of Presentation
      静岡市
    • Year and Date
      2006-07-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 膵β細胞の膨張により誘発されるインスリン分泌における伸展活性化カチオンチャネルの役割2006

    • Author(s)
      須之内 孝明
    • Organizer
      第52回日本薬学会東海支部総会・大会
    • Place of Presentation
      静岡市
    • Year and Date
      2006-07-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ラット後大脳動脈圧誘発性収縮におけるプロテインキナーゼCとRhoキナーゼの役割2006

    • Author(s)
      柏原 俊英
    • Organizer
      第52回日本薬学会東海支部総会・大会
    • Place of Presentation
      静岡市
    • Year and Date
      2006-07-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] ラットを用いた局所性冷却誘発皮膚血流減少反応のin vivo解析:シナプス前P2X受容体の関与2006

    • Author(s)
      本多 正樹
    • Organizer
      第115回日本薬理学会関東部会
    • Place of Presentation
      静岡市
    • Year and Date
      2006-07-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 膵β細胞の膨張により誘発されるインスリン分泌への伸展活性化カチオンチャネルの関与2006

    • Author(s)
      須之内 孝明
    • Organizer
      第114回薬理学会関東部会
    • Place of Presentation
      千葉市
    • Year and Date
      2006-06-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] K_<ATP> channel-hldependent pathways involved in glucose-induced insulin secretion2006

    • Author(s)
      Tomohisa Ishikawa
    • Organizer
      第79回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2006-03-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Passive stretching produces Akt-and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice:A novel pharmacological strategy for controlling glucose metabolism2006

    • Author(s)
      Yoshihiko Ito
    • Organizer
      第79回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2006-03-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 局所性冷却誘発皮膚血流減少反応のラットを用いたin vivoでの解析:シナプス前P2X受容体の関与2005

    • Author(s)
      本多 正樹
    • Organizer
      第113回日本薬理学会関東部会
    • Place of Presentation
      千葉市
    • Year and Date
      2005-10-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] メカノトランスダクションと細胞反応:肺動脈の収縮制御における意義と脂肪細胞分化に及ぼす作用2005

    • Author(s)
      田辺 由幸
    • Organizer
      生体機能と創薬シンポジウム2005
    • Place of Presentation
      広島市
    • Year and Date
      2005-09-09
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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