EFFECTS OF THE PEPTIDE HP228 ON NERVE DISORDERS IN DIABETIC RATS

Motor and sensory nerve conduction velocities (MNCV and SNCV) were red uced in the sciatic nerve of rats after 4 weeks of untreated streptozo tocin-induced diabetes, and declined further during the following 4 we eks. Treating diabetic rats with the novel peptide HP228 had no effect on the decline of MNCV after the first 4 weeks of diabetes but attenu ated the decline in SNCV, HP228 treatment also prevented any further d ecline in MNCV or SNCV between weeks 4 and 8 of diabetes. Consequently , at the conclusion of the study, the nerve conduction velocities (NCV s) in treated rats were significantly (both P<.001) higher than in unt reated diabetic rats. Reduced nerve homogenate Na+,K+-adenosine tripho sphatase (ATPase) activity in diabetic rats was significantly (P < .05 ) increased by HP228 but remained significantly (P < .05) lower than i n untreated controls. HP228 treatment also reduced nerve Na+,K+-ATPase activity of control rats compared with untreated controls (P < .05). There was no effect of HP228 on the hyperglycemia, nerve polyol accumu lation, myo-inositol depletion, reduced nerve laser Doppler blood flow , thermal hypoalgesia, or reduced mean axonal caliber in diabetic rats or on any of these parameters in control rats. These data demonstrate that a novel peptide may protect against the slowing of nerve conduct ion in prolonged diabetes and that the mechanism of action is unrelate d to aldose reductase inhibition, prevention of nerve ischemia, or axo nal atrophy. HP228 may prove a potential therapeutic agent for the tre atment of prolonged diabetic neuropathy. Copyright (C) 1998 by W.B. Sa unders Company.