Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat

Int J Exp Diabetes Res. 2001;2(3):187-93. doi: 10.1155/edr.2001.187.

Abstract

In order to explore the neuroprotective and cross-species activities of C-peptide on type 1 diabetic neuropathy, spontaneously diabetic BB/W-rats were given increasing doses of human recombinant C-peptide (hrC-peptide). Diabetic rats received 10, 100, 500, or 1000 microg of hrC-peptide/kg body weight/day from onset of diabetes. After 2 months of hrC-peptide administration, 100 microg and greater doses completely prevented the nerve conduction defect, which was associated with a significant but incomplete prevention of neural Na+/K+-ATPase activity in diabetic rats with 500 microg or greater C-peptide replacement. Increasing doses of hrC-peptide showed increasing prevention of early structural abnormalities such as paranodal swelling and axonal degeneration and an increasing frequency of regenerating sural nerve fibers. We conclude that hrC-peptide exerts a dose dependent protection on type 1 diabetic neuropathy in rats and that this effect is probably mediated by the partially conserved sequence of the active C-terminal pentapeptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • C-Peptide / pharmacology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetic Neuropathies / physiopathology
  • Diabetic Neuropathies / prevention & control*
  • Dose-Response Relationship, Drug
  • Humans
  • Insulin / therapeutic use
  • Kinetics
  • Male
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Neural Conduction / drug effects
  • Neural Conduction / physiology*
  • Rats
  • Rats, Inbred BB
  • Recombinant Proteins / blood
  • Recombinant Proteins / pharmacology
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Sural Nerve / drug effects
  • Sural Nerve / physiopathology

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin
  • Recombinant Proteins
  • Sodium-Potassium-Exchanging ATPase