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.


CONCLUSIONS
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.
Zhang
Weixian
W
Department of Pathology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Kamiya
Hideki
H
Ekberg
Karin
K
Wahren
John
J
Sima
Anders A F
AA
D000818:Animals; D002096:C-Peptide / Q000008:administration & dosage / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011913:Rats, Inbred BB
D002096:C-Peptide