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2003 Fiscal Year Final Research Report Summary

Study on multimolecular modulations of ATP-sensitive K^+ channels in pancreatic β-cells and their disharmony in diabetes.

Research Project

Project/Area Number 14571083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionAkita University

Principal Investigator

KAKEI Masafumi  Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (90214270)

Co-Investigator(Kenkyū-buntansha) ITO Seiki  Akita University, School of Medicine, Professor, 医学部, 教授 (40126389)
YADA Toshihiko  Jichi Medical College, School of Medicine, Professor, 医学部, 教授 (60166527)
Project Period (FY) 2002 – 2003
Keywordsinsulin secretion / K-ATP channels / sulfonylureas / membrane phospholipid / β-cells / receptor operation / ATP / diabetes mellitus
Research Abstract

ATP-sensitive K^+ (KATP) channels, composed of heteromultimers of sulfonylurea-receptor unit and a pore unit of inwardly rectifying K^+ channels, were studied with respect to effects of intracellular Ca^<2+> activity of the channels. It was found that elevation of intracellular Ca^<2+> conferred inhibition of functional transduction between binding of sulfonylureas to their receptors and closure of channels. Exposure of membrane patches to PIP_2 increased activity of KATP channels in association with reduction of ATP sensitivity of the channels. When measured membrane PIP_2 concentration by means of GFP (green fluorescent protein) labeled PH-domain contained probe, membrane fraction of GFP intensity decreased on exposure of β-cells to acetylcholine. The ATP sensitivity of the channel recorded in the presence of acetylcholine in the pipette in inside-out mode was increased as compared to that in control pipette solution. Acetylcholine, when it was applied to β-cell during cell-attached patch experiments, induced action currents. In whole-cell current recorded by nystatin-perforated mode, acetylcholine decreased the KATP channel currents at the glucose concentration of 2.8 mM. From these results, it is suggested that receptor-stimulation of pancreatic β-cells produces reduction of activity of the KATP channels associated with depolarization of membrane and an increase in output of insulin secretion around threshold concentrations of glucose. It is needed to further explore whether β-cells from diabetic animals have the inability of acetylcholine to depolarize the membrane and resultant perturbation of insulin secretion during parasympathetic neural stimulation.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Kakei M.: "Receptor-operated regulation of ATP-sensitive K^+ channels via membrane phospholipid metabolism"Current Medicinal Chemistry. 10. 235-243 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kakei M.: "Glucagon-like peptide-1 (GLP-1) evokes action potentials and increases cytosolic Ca^<2+> in rat nodose ganglion neurons."Autonomic Neuroscience : Basic and Clinical. 102. 39-44 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oketani N.: "Regulation of ATP-sensitive K^+ channels by P2Y-purinoceptors coupled to PIP_2 metabolism in guinea-pig ventricular cells."Am.J.Physiol.. 282. H757-H765 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakazaki M.: "Association of up-regulated activity of K_<ATP> channels with impaired insulin secretion in UCP1-expressing MIN6 cells"J.Physiol. 540.3. 781-789 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加計正文: "インスリン分泌のイオンチャネル機構と神経性調節"内分泌・糖尿病科. 17. 526-534 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加計正文: "膵β細胞代謝障害とインスリン分泌不全"「日本臨床」2002年増巻号 「新時代の糖尿病学1」-病因・診断・治療研究の進歩-日本臨床社. 504-510 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加計正文: "インスリン分泌のイオンチャネル機構"「日本臨床」2002年増巻号 「新時代の糖尿病学1」-病因・診断・治療研究の進歩-日本臨床社. 180-188 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kakei M: "Biochemistry : ATP-sensitive K^+ channels, insulin secretion and diabetes"Research Signpost, Kerala, India (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 加計正文: "Annual Review内分泌・代謝、インスリン分泌の分子機構"中外医学社. 294 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kakei M.: "Receptor-operated regulation of ATP-sensitive K^+ channels via membrane phospholipid metabolism"Current Medicinal Chemistry. 10. 235-243 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakei M.: "Glucagon-like peptide-1 (GLP-1) evokes action potentials and increases cytosolic Ca^<2+> in rat nodose ganglion neurons."Autonomic Neuroscience : Basic and Clinical. 102. 39-44 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakazaki, M.: "Association of up-regulated activity of K_<ATP> channels with impaired insulin secretion in UCP1-expressing MIN6 cells"J.Physiology. 540.3. 781-789 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oketani, N.: "Regulation of ATP-sensitive K^+ channels by P2Y-purinoceptors coupled to PIP_2 metabolism in guinea-pig ventricular cells"Am J Physiol.. 282(2). H757-H765 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakei, M.: "Ion channel mechanism of insulin secretion and neural regulation.(Japanese)"Endocrine and diabetes.. 17. 526-534 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakei M.: "Failure of insulin secretion and metabolic perturbation in pancreatic b-cells(Japanese)"Progress of pathogenesis, diagnosis and therapy in new trend in diabetes 1.(Nihonrinsho Co.). 504-510 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakei M.: "Ion channels in insulin secretion.(Japanese)"Progress of pathogenesis, diagnosis and therapy in new trend in diabetes 1.(Nihonrinsho Co.). 180-183 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakei M.: "Molecular mechanism of insulin secretion (Japanese)"Annual Review of Endocrinology and Metabolism,(Chugai Igakusha.). 294 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kakei M.: "ATP-sensitive K channels, insulin secretion and diabetes. Tentative title "Biochemistry"."Research Signpost Co. Ltd, Kerala, India(in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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