DIABETIC NEUROPATHY IN SUCROSE-FED OTSUKA LONG-EVANS TOKUSHIMA FATTY RATS - EFFECT OF AN ALDOSE REDUCTASE INHIBITOR, TAT

In an animal model of human non-insulin dependent diabetes mellitus (N IDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with su crose for 8 weeks to obtain severe hyperglycemia. The effects of sucro se administration on peripheral nerve functions, motor nerve conductio n velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood f low (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLET F rats caused significant body weight reduction and remarkable hypergl ycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV , decreased CVR-R, reduced SNBF and increased platelet aggregation act ivity to ADP. Sorbitol and fructose accumulation, and myo-inositol dep letion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. T hese observations suggest that the sucrose-fed OLETF rat is a useful a nimal model for studying the pathogenesis of diabetic neuropathy in hu man NIDDM, and that an aldose reductase inhibitor is a useful therapeu tic agent for the treatment of diabetic neuropathy.