C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes.
We examined the effects of C-peptide replacement on unmyelinated fiber function in the hind paw, sural nerve C-fiber morphometry, sciatic nerve neurotrophins, and the expression of neurotrophic receptors and content of neuropeptides in dorsal root ganglia in type 1 diabetic BB/Wor-rats. C-peptide replacement from onset of diabetes had no effect on hyperglycemia, but it significantly prevented progressive thermal hyperalgesia and prevented C-fiber atrophy, degeneration, and loss. These findings were associated with preventive effects on impaired availability of nerve growth factor and neurotrophin 3 in the sciatic nerve and significant prevention of perturbed expression of insulin, insulin growth factor-1, nerve growth factor, and neurotrophin 3 receptors in dorsal root ganglion cells. These beneficial effects translated into prevention of the decreased content of dorsal root ganglia nociceptive peptides such as substance P and calcitonin gene-related peptide. From these findings we conclude that replacement of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The data indicate that perturbed insulin/C-peptide action plays an important pathogenetic role in nociceptive sensory neuropathy and that C-peptide replacement may be of benefit in treating painful diabetic neuropathy in insulin-deficient diabetic conditions.
Kamiya
Hideki
H
Department of Pathology, Wayne State University, School of Medicine, Detroit, MI, USA.
Zhang
Weixian
W
Sima
Anders A F
AA
D000818:Animals; D002096:C-Peptide / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000150:complications / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB
D002096:C-Peptide