Metabolism - Clinical and Experimental
Volume 47, Issue 6 , Pages 650-656, June 1998

Effects of the peptide HP228 on nerve disorders in diabetic rats☆

  • Nigel A. Calcutt

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Nigel A. Calcutt, PhD, Department of Pathology, University of California, San Diego, La Jolla, CA 92093-0612.
    • Department of Pathology, University of California, San Diego, La Jolla, USA
    • Veterans Administration Medical Center, San Diego, CA, USA
    • ,
  • Kevin C. Dines

      Affiliations

    • Department of Pathology, University of California, San Diego, La Jolla, USA
    • Veterans Administration Medical Center, San Diego, CA, USA
    • ,
  • Rose M. Ceseña

      Affiliations

    • Department of Pathology, University of California, San Diego, La Jolla, USA
    • Veterans Administration Medical Center, San Diego, CA, USA

Received 17 March 1997; accepted 12 December 1997.

Abstract 

Motor and sensory nerve conduction velocities (MNCV and SNCV) were reduced in the sciatic nerve of rats after 4 weeks of untreated streptozotocin-induced diabetes, and declined further during the following 4 weeks. Treating diabetic rats with the novel peptide HP228 had no effect on the decline of MNCV after the first 4 weeks of diabetes but attenuated the decline in SNCV. HP228 treatment also prevented any further decline in MNCV or SNCV between weeks 4 and 8 of diabetes. Consequently, at the conclusion of the study, the nerve conduction velocities (NCVs) in treated rats were significantly (both P < .001) higher than in untreated diabetic rats. Reduced nerve homogenate Na+,K+-adenosine triphosphatase (ATPase) activity in diabetic rats was significantly (P < .05) increased by HP228 but remained significantly (P < .05) lower than in 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 accumulation, 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 conduction in prolonged diabetes and that the mechanism of action is unrelated to aldose reductase inhibition, prevention of nerve ischemia, or axonal atrophy. HP228 may prove a potential therapeutic agent for the treatment of prolonged diabetic neuropathy.

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☆ Supported by Trega Biosciences.

PII: S0026-0495(98)90025-7

Metabolism - Clinical and Experimental
Volume 47, Issue 6 , Pages 650-656, June 1998

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