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Physiological and molecular biological studies on altered function of the intracellular signal transduction system in pancreatic beta cells of diabetes mellitus.

Research Project

Project/Area Number 03671145
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

ISHIDA Hitoshi  Assistant Professor, Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, 医学部, 助手 (80212893)

Co-Investigator(Kenkyū-buntansha) TSUDA Kinsuke  Associate Professor, Department of Integrated Human Sciences, Kyoto University, 総合人間学部, 助教授 (10180001)
SEINO Yutaka  Associate Professor, Department of Metabolism and Clinical Nutrition, Kyoto Univ, 医学部, 助教授 (40030986)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsDiabetes mellitus / Intracellular signal transduction system / Intracellular calcium concentration / insulin / ATP-sensitive K^+ channel / Voltage-dependent Ca^<2+> channel / Patch-clamp technique / ATP感受性K^+チャネル / 電位依存性Ca^<2+>チャネル / 膵β細胞 / 細胞内カルシウム / イオンチャネル
Research Abstract

In order to elucidate the intracellular mechanisms of impaired insulin secretion induced by glucose from pancreatic beta cells in diabetes mellitus, the altered functions of intracellular calcium signaling system and ion channels were investigated using beta cells obtained from rats of experimentally-induced non-insulin-dependent diabetes mellitus (NIDDM), or those exposed to high glucose in vitro. The glucose-induced insulin release is significantly reduced in these cells compared to the controls. In addition, the intracellular calcium ([Ca^<2+>]i) response is similarly decreased after the glucose loading. These facts clearly indicate that the abnormalities in intracellular calcium signaling system in beta cells is closely related to the impaired insulin secretion induced by glucose in NIDDM. To further elucidate the pathogenesis of reduced [Ca^<2+>]i response, the properties of ATP sensitive K^+ channel (K_<ATP> channel) was studied in NIDDM rats using the patch-clamp technique. The inhibitory effect of glucose on beta cell K_<ATP> channel activities is significantly impaired in NIDDM rats compared to the controls, but the ATP sensitivity is identical between them. The glucose insensitivity of K_<ATP> channels is, therefore, probably due to an insufficient ATP production caused by impaired glucose metabolism in beta cells of NIDDM. The insufficient depolarization of beta cell plasma membrane due to the reduced inhibition of K_<ATP> channel activities seems to cause the decreased [Ca^<2+>]i elevation in NIDDM beta cells, leading to the impaired isulin secretion induced by glucose.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Y.Tsuura: "Impaired glucose sensitivity of ATP-sensitive K_+ channels in pancreatic β cells in streptozotocin-induced NIDDM rats." Diabetes. 41. 861-865 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Okamoto: "The role of cytosolic Ca_<2+> in impaired sensitivity to glucose of rat pancreatic islets exposed to high glucose in vitro" Diabetes. 41. 1555-1561 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kurose: "Glucagon,insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats.A study with the isolated perfused rat pancreas in vitro" Diabetes. 35. 1035-1041 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] S.Than: "Bone marrow transplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice." J.Exp.Med.176. 1233-1238 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N.Takeshita: "Circulating levels and bone contents of bone γ-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus." Acta Endocrinol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Tsuji: "Selective impairment of the cytoplasmic Ca_<2+> response to glucose in rat pancreatic β-cells of streptozotocin-induced non-insulin-dependent." Metabolism.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Tsuura, H.Ishida, Y.Okamoto, K.Tsuji, T.Kurose, M.Horie, H.Imura, Y.Okada, Y.Seino: "Impaired glucose sensitivity of ATP-sensitive K^+ channels in pancreatic beta cells in streptozotocin-induced NIDDM rats." Diabetes. 41(7). 861-865 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Okamoto, H.Ishida, T.Taminato, K.Tsuji, T.Kurose, Y.Tsuura, S.Kato, H.Imura, Y.Seino: "The role of cytosolic Ca^<2+> in impaired sensitivity to glucose of rat pancreatic islets exposed to high glucose in vitro." Diabetes. 41(12). 1555-1561 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kurose, K.Tsuda, H.Ishida, K.Tsuji, Y.Okamoto, Y.Tsuura, S.Kato, M.Usami, H.Imura, Y.Seino: "Glucagon, insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats." Diabetologia. 35. 1035-1041 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] S.Than, H.Ishida, M.Inaba, Y.Fukuda, Y.Seino, M.Adachi, H.Imura, S.Ikehara: "Bone marrow transplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice." J. Exp. Med.176(10). 1233-1238 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N.Takeshita, H.Ishida, T.Yamamoto, G.Koh, T.Kurose, K.Tsuji, Y.Okamoto, H.Ikeda, Y.Seino: "Circulating levels and bone contents of bone gamma-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus." Acta Endocrinol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Tsuji, T.Taminato, H.Ishida, Y.Okamoto, Y.Tsuura, S.Kato, T.Kurose, Y.Okada, H.Imura, Y.Seino: "Selective impairment of the cytoplasmic Ca^<2+> response to glucose in rat pancreatic beta-cells of streptozotocin-induced non-insulin-dependent diabetes." Metabolism.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Tsuura: "Impaired glucose sensitivity of ATP-sensitive K^+ channels in pancreatic β cells in streptozotocin-induced NIDDM rats." Diavetes. 41. 861-865 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Okamoto: "The role of cytosolic Ca2^+ in impaired sensitivity to glucose of rat pancreatic islets exposed to high glucose in vitro." Diabetes. 41. 1555-1561 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kurose: "Glucagon,insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats.A study with the isolated perfused rat pancreas in vitro." Diabetologia. 35. 1035-1041 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Than: "Bone marrow sransplantation as a strategy for treatment of non-insulin-dependent diabetes mellitus in KK-Ay mice." J.Exp.Med.176. 1233-1238 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Takeshita: "Circulating levels and bone contents of bone r-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus." Acta Endocrinol.

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Tsuji: "Selective impairment of the cytoplasmic Ca2^+ response to glucose in rat pancreatic β-cells of streptozotocin-induced non-insulin-dependent." Metabolism.

    • Related Report
      1992 Annual Research Report
  • [Publications] Yoshimasa Okamoto et al.: "The Role of Cytosolic Ca^<2+> in Impaired Sensitivity to Glucose of Rat Pancreatic Islets Exposed to High Glucose In Vitro" Diabetes.

    • Related Report
      1991 Annual Research Report
  • [Publications] Yoshiyuki Tsuura et al.: "Impaired Glucose Sensitivity of ATPーSensitive K^+ Channels in Pancreatic β Cells in StreptozotocinーInduced NIDDM Rats" Diabetes.

    • Related Report
      1991 Annual Research Report
  • [Publications] Kazuo Tsuji et al.: "Selective Impairment of the Cytoplssmic Ca^<2+> Response to Glucose in pancreatic βーcells of the NIDDM Rat Model" Diabetologia.

    • Related Report
      1991 Annual Research Report
  • [Publications] Kazuo Tuji et al.: "Cytoplasmic Ca^<2+> Rosponse in Pancreatic β cells of NON mice" Current Concepts of a New Animal Model NON Mouse.

    • Related Report
      1991 Annual Research Report
  • [Publications] Takeshi Kurose et al.: "Glucagon,Insulin,and somatostatin secretion in response to sympathetic neural activation in NIDDM and IDDM rats induced by streptozotocin:A study with the isolated perfused rat panereaト in vitro" Diabetes.

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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