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Studies on the pathogenesis and treatment of diabetic neuropahy ; mechanisms of impaired regeneration of peripheral nerve and tiral for its inhibition

Research Project

Project/Area Number 04671455
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionHirosaki University

Principal Investigator

YAGIHASHI Soroku  Hirosaki Univ SCH of MED, Professor, 医学部, 教授 (40111231)

Co-Investigator(Kenkyū-buntansha) ONUMA Tomio  Hirosaki Univ SCH of MED, Associate Professor, 医学部, 助教授 (00150251)
BABA Masayuki  Hirosaki Univ SCH of MED, Associate Professor, 医学部, 助教授 (90106849)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsDiabetes mellitus / Neuropathy / Regeneration / Morphometry / Nerve grouwth factor / Neurofilament / Axonal degeneration
Research Abstract

Impaired regeneration of peripheral nerve was exmained in the severed peripheral nerve of streptozotocin (STZ)-induced diabetic rats with light and electron microscopic morphometrical analysis. Immunocytochemical evaluation on the expression of nerve growth factor receptor (NFGR) was also conducted. For the further elucidation of mechanisms of impaired regeneration, Northern blot analysis on mRNA levels of neurofilament (NF-68) was also performed. In addition to these experimental studies, preliminary examinations on the human biopsied sural nerve samples to determine the NGFR expression were also undertaken.
Diabetic rats showed significant reduction of mean size of regenerated nerve fibers and axon/fiber size ratio, but there was no significant difference in the number, density of regenerated myelinated nerve fibers between diabetic and normal control rats during 2-4weeks experiments after nerve section. NGFR expression was reduced in diabetic rats only at the point of 4 weeks after the section of the nerve. NF-68 mRNA expression was significantly reduced in diabetic rats as compared with normal control rats. The impaired regeneration was represented by the thin myelinated fibers which are probably related to the reduced synthesis of axonal neurofilaments. NGFR expression appeared to correlate to this abnormality. Human diabetic nerves showed high expression of NGFR similar to other axonal type of neuropathy. Thus the NGFR-NF synthesis seems to be the crucial step for the perturbation of nerve regeneration in diabetes.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 八木橋操六: "Axonal cytoskeleton and diabetic neuropathy." Diabetic Medicine. 10. 107-109 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 八木橋操六: "Peripheral neuropathy in the WBN/Kob rat with spontaneous diabetes and pancreatitis" Laboratory Investigation. 68. 296-307 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 八木橋操六: "糖尿病の細胞生物学-糖尿病と末梢神経-" 細胞. 25. 174-179 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 八木橋操六: "AGE(Glycation)と神経障害" Diabetes Frontier. 4. 421-426 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yagihasi S.: "Axonal cytoskeleton and diabetic neuropathy" Diabetic medicine. Vol.10. 107-109 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yagihashi, S et al.: "Peripehral neuropathy in the WBN/Kob rat with spontaneous diabetes and pancreatitis" Laboratory Investigation. Vol.68. 296-307 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yagihashi S.: "Cell biology of diabetes-diabetes and peripheral nerve" Saibo(Cell)(Japanese). Vol.25. 174-179 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yagihashi S.: "AGE(Glycation) and diabetic neuropathy" Diabetes Frontier. Vol.4. 421-426 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 八木橋操六: "Axonal cytoskeleton and diabetic neuropathy." Diabetic Medicine. 10. 107-109 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 八木橋操六: "Peripheral neuropathy in the WBN/Kob rat with spontaneous diabetes and pancreatitis" Laboratory Investigation. 68. 296-307 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 八木橋操六: "糖尿病の細胞生物学-糖尿病と末梢神経-" 細胞. 25. 174-179 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 八木橋操六: "AGE(Glycation)と神経障害" Diabetes Frontier. 4. 421-426 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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