Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat.
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.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011913:Rats, Inbred BB; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013497:Sural Nerve / Q000187:drug effects / Q000503:physiopathology
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011994:Recombinant Proteins; D000254:Sodium-Potassium-Exchanging ATPase