Physiological and morphometric analyses of neuropathy in sucrose-fed OLETF rats
To investigate the characteristic features of diabetic neuropathy in type 2 diabetes mellitus, Otsuka Long–Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus, and non-diabetic Long–Evans Tokushima Otsuka (LETO) rats were fed with or without sucrose and/or an aldose...
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Veröffentlicht in: | Diabetes research and clinical practice 2001, Vol.51 (1), p.9-20 |
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Sprache: | eng |
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Zusammenfassung: | To investigate the characteristic features of diabetic neuropathy in type 2 diabetes mellitus, Otsuka Long–Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus, and non-diabetic Long–Evans Tokushima Otsuka (LETO) rats were fed with or without sucrose and/or an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), for 24 weeks, and physiological, biochemical and morphological assessments were performed. Sucrose administration caused remarkable hyperglycemia in OLETF rats but not in LETO rats. Sucrose-fed OLETF rats demonstrated delayed nerve conduction velocity, decreased coefficient of variation of R-R interval, reduced sciatic nerve blood flow, increased platelet aggregation activity, a lower concentration of erythrocyte 2,3-diphosphoglycerate, and decreased Na
+/K
+-ATPase activity in sciatic nerves, compared with the non-sucrose-fed OLETF and LETO rats. TAT prevented all these deficits except hyperglycemia. Sorbitol and fructose accumulation and
myo-inositol depletion in tail nerves of sucrose-fed OLETF rats were ameliorated by TAT. Myelinated fiber size and density in sural nerves of sucrose-fed OLETF rats were decreased and increased, respectively, compared with non-sucrose-fed OLETF and LETO rats. These morphological abnormalities were normalized by TAT. These observations suggest that the sucrose-fed OLETF rat developed diabetic neuropathy not only electrophysiologically but also histologically, and that an aldose reductase inhibitor, TAT, possesses therapeutic value for the treatment of diabetic neuropathy. |
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ISSN: | 0168-8227 1872-8227 |
DOI: | 10.1016/S0168-8227(00)00205-9 |