2003 Fiscal Year Final Research Report Summary
Diabetic neuropathy in mice transgenic for human aldose reductase.
| Project/Area Number |
14571081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Hirosaki University |
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Principal Investigator |
YAMAGISHI Shin-ichiro Hirosaki Univ.School of Medicine, Pathology, Assistant, 医学部, 助手 (80301026)
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| Project Period (FY) |
2002 – 2003
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| Keywords | aldose reductase / diabetic complication / protein kinase C / transgenic mice / diabetic neuropathy / polyol pathway |
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| Research Abstract |
To explore the relationship between polyol pathway and protein kinase C(PKC), we examined PKC activities and expressions of PKC isoforms separately in endoneurial and vesse1-rich epineurial tissues in diabetic mice transgenic for human aldose reductase(Tg). Tg and littermate control mice(Lm) were made diabetic by streptozotocin at 8 weeks of age and treated with aldose reductase inhibitor(ARI) (fidarestat 4mg/kg/day, per os) or placebo for 12 weeks. At end, compared to non-diabetic state, sorbitol contents were increased 6.4 fold in endoneurium and 5.1 fold in epineurium in diabetic Tg, whereas the increase was detected only in endoneurium in diabetic Lm. Endoneurial PKC activity was significantly reduced in diabetic Tg. By contrast, epineurial PKC activity was increased in both diabetic Lm and diabetic Tg and there was no significant difference between the two groups. These changes were all corrected by ARI treatment. Consistent with the changes of PKC activities, diabetic Tg showed decreased expression of PKC a in endoneurium, whereas there was an increased expression of PKC β II in epineurium in both diabetic Tg and diabetic Lm. These findings suggest the presence of dichotomous metabolic pathway between neural and vascular tissues in the polyol-PKC-related pathogenesis of diabetic neuropathy.
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Research Products
(4 results)
