Physiological and morphometric analyses of neuropathy in sucrose-fed OLETFrats

To investigate the characteristic features of diabetic neuropathy in type 2 diabetes mellitus, Otsuka Long-Evans Tokushima fatty (OLETF) rats, an anim al model of human type 2 diabetes mellitus, and non-diabetic Long-Evans Tok ushima 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 ner ve 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-fe d OLETF and LETO rats. TAT prevented all these deficits except hyperglycemi a. Sorbitol and fructose accumulation and inyo-inositol depletion in tail n erves of sucrose-fed OLETF rats were ameliorated by TAT. Myelinated fiber s ize and density in sural nerves of sucrose-fed OLETF rats were decreased an d increased, respectively, compared with non-sucrose-fed OLETF and LETO rat s. These morphological abnormalities were normalized by TAT. These observat ions suggest that the sucrose-fed OLETF rat developed diabetic neuropathy n ot only electrophysiologically but also histologically, and that an aldose reductase inhibitor, TAT, possesses therapeutic value for the treatment of diabetic neuropathy. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.