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RESEACH FOR THE PATHOGENIC MECHANISM OF DIABETIC NEUROPATHY

Research Project

Project/Area Number 12671107
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKAMURA Jiro  Graduate School of Mpdicine, Nagoya University, Associate Professor, 大学院・医学研究科, 助教授 (40283444)

Co-Investigator(Kenkyū-buntansha) NAKASHIMA Eitaro  University Hospital, Nagoya University, Research Associate, 医学部・附属病院, 助手 (50335030)
HAMADA Yoji  University Hospital, Nagoya University, Research Associate, 医学部・附属病院, 助手 (20293706)
茶谷 貞男  名古屋大学, 医学部, 助手 (30313993)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsDiabetic Neuropathy / Schwannoma Celis / Polyol Pahtway / Protein Kinase C / Aldosb Reduclase Inhibitior / プロティンキナーゼC
Research Abstract

Aims : Polyol pathway hyperactivity and altered PKC activity have been proposed as the pathogenic mechanism of diabetic neuropathy. However, the relationship between polyol pathway and PKC activity has not been precisely investigated. The present study was conducted to investigate the effects of high glucose and polyol pathway on the PKC-MAPK cascade and cell growth using.cultured rat Schwannoma cells (JS-1 cells).Methods : JS-1 cells were cultured in 5.5 or 20 mM glucose (HG) with or without epalrestat (Ep ; 1μM) for 14 days, or treated with an antisense against PKC-α (AS) or a p38 MAPK specific inhibitor, SB-203580 (SB). The proliferation activity by assay of [^3H]-thyraidine uptake (% of control), PKCα activity by its protein expression in membrane fraction, and p38 activity by the ratio of phosphorylated to total p38 protein expression were measured.Results : 1) PKC-a and p38 activityies were decreased under the HG condition, which were ameliorated by Ep. 2) With AS treatment, the protein expression of PKC-α and p3S activity were decreased in a time- and dose-dependent fashion. 3) Proliferation activity was decreased by both AS and SB in a dose-dependent fashion. Conclusions: These results suggest that PKC-α and p38 MAPK activities are decreased by high glucose through the alclose reductase-sensit.ive pathway, and that PKC-α-p38 cascade would play an important- role in proliferation of neural cells, indicating,that glucose-induced polyol. Pathway hyperactivity would deteriorate the proI.ifernIion of Sdiwmm cells through' the decreased activities of PKC-α and p38 MAPK, leading t.o diabetic neuropathy.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Hamada Y: "Epalrestat, an aldose reductase inhibitor, reduces the levels of N^ε-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients"Diabetes Care. 23. 1539-1544 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naruse K: "Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes"Exp Eye Res.. 71. 309-315 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura J: "Physiologiacal and morphometric analyses of neuropathy in sucrose-fed OLETF rats"Diabetes Res Clin Pract. 51. 9-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuda Y: "Role of PKC and TGF-β receptor in glucose-induced proliferation of smooth muscle cells"Biochem Biophys Res Commun.. 281. 71-77 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura J: "Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity"Diabetologia. 44. 480-487 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakayama M: "Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy"Diabetes Care. 24. 1093-1098 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hamada Y.: "Epalrestat, an aldose reductase. Inhibitor, reduces the levels of N'-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients"Diabetes Care. 23. 1539-1544 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naruse K.: "Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes"Exp Eye Res. 71. 309-315 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura J.: "Physiologiacal and morphometric analyses of neuropathy in sucrose-fed OLETF rats."Diabetes Res Clin Pract. 51. 9-20 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuda Y.: "Role of PKC and TGF-βreceptor in glucose-induced proliferation of smooth muscle cells"Biochem Biophys Res Commun. 281. 71-77 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakamura J.: "Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity"Diabetologia. 44. 480-487 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakayama M.: "Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy"Diabetes Care. 24. 1093-1098 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuda Y: "Role of PKC and TGF-β receptor in glucose-induced proliferation of smooth muscle cells"Biochem Biophys Res Commun. 281. 71-77 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura J: "Glucose-induced hyperproliferation of cultured rat aortic smooth muscle cells through polyol pathway hyperactivity"Diabetologia. 44. 480-487 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakayama M: "Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy"Diabetes Care. 24. 1093-1098 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jiro Nakamura: "Physiological and morphometric analysis of neuropathy in sucrose-fed OLETF rats"Elsevier Diabeles Research and Clinical Practice. 51. 9-20 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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