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The mechanism of glucose-induced time-dependent potentiation of insulin secretion from pancreatic β cells and its alteration in diabetic state

Research Project

Project/Area Number 13671186
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

FUJIMOTO Shimpei  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (00333576)

Co-Investigator(Kenkyū-buntansha) NAGASHIMA Kazuaki  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (40324628)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordspancreatic islet / pancreatic β cell / insulin secretion / glucose / priming effect / exocytotic system / intracellular Ca^<2+> concentration / intracelluar ATP concentration / ブドウ島
Research Abstract

A brief exposure to elevated glucose augments the insulin secretory response of islets to subsequent stimulation. The site of this time-dependent potentiation (priming effect) of glucose in the mechanism of the regulation of insulin secretion is not completely known, however. Insulin release triggered by a depolarizing concentration of K^+ in the presence of basal glucose is markedly enhanced in primed rat islets. To clarify the role of priming on Ca^<2+> and ATP efficacy in the exocytotic apparatus, islets were electrically permeabilized to vary the intracellular Ca^<2+> and ATP concentration according to the extracellular medium, and insulin release was evaluated. Ca^<2+ >and ATP efficacy in Ca^<2+> and ATP-dependent insulin secretion was not affected by priming, and alteration of the intracellular Ca^<2+> concentration after depolarization cannot account for the phenomenon. There was no difference in ATP content before depolarization between nonprimed and primed islets. Moreover, the decline in ATP level after depolarization with basal glucose was observed in both primed and nonprimed islets. However, a reduced decline in ATP level in the early phase was observed in primed islets. In addition, oligomycin, a mitochondrial metabolism inhibitor, abolished the difference in ATP level between primed and nonprimed islets, suggesting that mitochondrial ATP production may be linked to the phenomenon

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Kajikawa M, Fujimoto S et al.: "Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets"Diabetes. 51(8). 2522-2529 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyawaki K et al.(21名7番): "Inhibition of gastric inhibitory polypeptide signaling prevents obesity"Nature Medicine. 8(7). 738-742 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujimoto S et al.: "Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets"Endocrinology. 143(1). 213-221 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamamoto Y, Tsuura Y, Fujimoto S et al.: "Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation"Biochem Biophys Res Commun. 287(1). 104-109 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen ZP et al.(7名 4番): "Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets"Diabetes Res Clin Pract. 53(1). 9-16 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda T, Tsuura Y, Fujita J, Fujimoto S et al.: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commun. 284(1). 20-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kajikawa M, Fujimoto S et al.: "Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets"Diabetes. 51(8). 2522-2529 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyawaki K, Fujimoto S et al.: "Inhibition of gastric inhibitory polypeptide signaiing prevents obesity"Nature Medicine. 8(7). 738-742 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujimoto S et al.: "Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets"Endocrinology. 143(1). 213-221 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamamoto Y, Fujimoto S et al.: "Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation"Biochem Biophys Res Commun. 287(1). 104-109 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen ZP, Fujimoto S et al.: "Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets"Diabetes Res Clin Pract. 53(1). 9-16 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeda T, Fujimoto S et al.: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commun. 284(1). 20-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kajikawa M, Fujimoto S et al.: "Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets"Diabetes. 51(8). 2522-2529 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyawaki K et al.(21名7番): "Inhibition of gastric inhibitory polypeptide signaling prevents obesity"Nature Medicine. 8(7). 738-742 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujimoto S et al.: "Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets"Endocrinology. 143(1). 213-221 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamamoto Y, Tsuura Y, Fujimoto S et al.: "Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation"Biochem Biophys Res Commun. 287(1). 104-109 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shen ZP et al.(7名4番): "Distinct effect of diazoxide on insulin secretion stimulated by protein kinase A and protein kinase C in rat pancreatic islets"Diabetes Res Chin Pract. 53(1). 9-16 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeda T, Tsuura Y, Fujita J, Fujimoto S et al.: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commun. 284(1). 20-25 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujimoto S et al.: "Prior exposure to high glucose augments depolarization-induced insulin release by mitigating the decline of ATP level in rat islets"Endocrinology. 143・1. 213-221 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hamamoto Y, Tsuura Y, Fujimoto S et al.: "Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation"Biochem Biophys Res Commun. 287・1. 104-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shen ZJ et al.(7名 4番): "Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation"Diabetes Res Clin Pract. 53・1. 9-16 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeda T, Tsuura Y, Fujita J, Fujimoto S et al.: "Heat shock restores insulin secretion after injury by nitric oxide by maintaining glucokinase activity in rat islets"Biochem Biophys Res Commum. 284・1. 20-25 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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