Premium
C‐peptide improves neuropathy in type 1 diabetic BB/Wor‐rats
Author(s) -
Zhang Weixian,
Kamiya Hideki,
Ekberg Karin,
Wahren John,
Sima Anders A. F.
Publication year - 2007
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.672
Subject(s) - peptide , diabetic neuropathy , medicine , c peptide , endocrinology , chemistry , diabetes mellitus , biochemistry
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. Copyright © 2006 John Wiley & Sons, Ltd.