C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats

BACKGROUND: The spontaneously diabetic BB/Wor-rat is a close model of human type 1 diabetes and develops diabetic polyneuropathy (DPN) similar to that seen in type 1 patients. Here we examine the therapeutic effects of C-peptide, delivered as continuous infusion or once daily subcutaneous injections on established DPN. METHODS: Diabetic rats were treated from four to seven months duration of diabetes with full continuous replacement dose of rat C-peptide via (a) osmopumps (OS), (b) full replacement dose (HSC) or (c) one-third of full replacement dose (LSC) by once daily injections. RESULTS: Diabetic rats treated with OS showed improvements in motor nerve conduction velocity (p < 0.001), sural nerve myelinated fibre number (p < 0.005), size (p < 0.05), axonal area (p < 0.001), regeneration (p < 0.001) and overall neuropathy score (p < 0.001). The progressive decline in sensory nerve conduction velocity was fully prevented. The frequencies of Wallerian degeneration were decreased (p < 0.005). HSC-treated rats showed prevention of further progression of DPN (p < 0.001), whereas LSC-treated rats showed a milder progression of DPN (p < 0.001) compared to untreated rats as assessed by neuropathy score. CONCLUSION: We conclude that (1) C-peptide is effective in the treatment of established DPN, (2) its effect is dose-dependent and (3) replacement by continuous infusion is the most effective administration of C-peptide.