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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 12
pubmed:dateCreated
2001-11-9
pubmed:abstractText
The present study was designed to examine the effect of aldose reductase (AR) overexpression on the development of diabetic neuropathy by using mice transgenic for human AR. At 8 weeks of age, transgenic mice (Tg) and non-transgenic littermates (Lm) were made diabetic with streptozotocin. After 8 weeks of untreated diabetes, plasma glucose levels and the reduction in body weight were similar between the groups of diabetic animals. Despite the comparable levels of hyperglycaemia, levels of sorbitol and fructose were significantly greater in the peripheral nerve of diabetic Tg than in diabetic Lm (both P < 0.01). Ouabain sensitive Na(+),K(+)-ATPase activity was similarly decreased in both diabetic Tg and Lm. Protein kinase C activity in the sciatic nerve membrane fraction was unaffected by diabetes in Lm, but was reduced by nearly 40% in the diabetic Tg. Although both groups of diabetic animals exhibited a significant decrease in tibial nerve motor nerve conduction velocity (MNCV), this decrease was significantly more severe (P < 0.01) in diabetic Tg than in diabetic Lm. Consistent with these findings, nerve fibre atrophy was significantly more severe in diabetic Tg than in diabetic Lm (P < 0.01). These findings implicate increased polyol pathway activity in the pathogenesis of diabetic neuropathy. In support of this hypothesis, treating diabetic Tg with an aldose reductase inhibitor (WAY121-509, 4 mg/kg/day) for 8 weeks significantly prevented the accumulation of sorbitol, the decrease in MNCV and the increased myelinated fibre atrophy in diabetic Tg.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-8950
pubmed:author
pubmed:issnType
Print
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2448-58
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11701599-Aldehyde Reductase, pubmed-meshheading:11701599-Animals, pubmed-meshheading:11701599-Diabetes Mellitus, Experimental, pubmed-meshheading:11701599-Diabetic Neuropathies, pubmed-meshheading:11701599-Enzyme Inhibitors, pubmed-meshheading:11701599-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:11701599-Female, pubmed-meshheading:11701599-Glucose, pubmed-meshheading:11701599-Humans, pubmed-meshheading:11701599-Hyperglycemia, pubmed-meshheading:11701599-Mice, pubmed-meshheading:11701599-Mice, Inbred C57BL, pubmed-meshheading:11701599-Mice, Inbred DBA, pubmed-meshheading:11701599-Mice, Transgenic, pubmed-meshheading:11701599-Motor Neurons, pubmed-meshheading:11701599-Neural Conduction, pubmed-meshheading:11701599-Protein Kinase C, pubmed-meshheading:11701599-Sciatic Nerve, pubmed-meshheading:11701599-Sodium-Potassium-Exchanging ATPase
pubmed:year
2001
pubmed:articleTitle
Neuropathy in diabetic mice overexpressing human aldose reductase and effects of aldose reductase inhibitor.
pubmed:affiliation
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan. yagihasi@cc.hirosaki-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't