Vol 8, No 5 (2007): Practical Diabetology
Other materials agreed with the Editors
Published online: 2007-05-24
C-peptide reverses nociceptive neuropathy in type 1 diabetes
Diabetologia Praktyczna 2007;8(5):178-187.
Abstract
We examined the therapeutic effects of C-peptide
on established nociceptive neuropathy in type 1 diabetic
BB/Worrats. Nociceptive nerve function, unmyelinated
sural nerve fiber and dorsal root ganglion
(DRG) cell morphometry, nociceptive peptide content,
and the expression of neurotrophic factors and
their receptors were investigated. C-peptide was
administered either as a continuous subcutaneous
replacement dose via osmopumps or a replacement
dose given once daily by subcutaneous injection.
Diabetic rats were treated from 4 to 7 months of
diabetes and were compared with control and untreated
diabetic rats of 4- and 7-month duration. Osmopump
delivery but not subcutaneous injection improved hyperalgesia and restored the diabetesinduced
reduction of unmyelinated fiber number
(p < 0.01) and mean axonal size (p < 0.05) in the
sural nerve. High-affinity nerve growth factor (NGF)
receptor (NGFR-TrkA) expression in DRGs was significantly
reduced at 4 months (p < 0.01). Insulin receptor
and IGF-I receptor (IGF-IR) expressions in DRGs
and NGF content in sciatic nerve were significantly
decreased in 7-month diabetic rats (p < 0.01, 0.05,
and 0.005, respectively). Osmopump delivery prevented
the decline of NGFR-TrkA, insulin receptor
(p < 0.05), and IGF-IR (p < 0.005) expressions in DRGs
and improved NGF content (p < 0.05) in sciatic nerve.
However, subcutaneous injection had only marginal
effects on morphometric and molecular changes
in diabetic rats. We conclude that C-peptide
exerts beneficial therapeutic effects on diabetic
nociceptive neuropathy and that optimal effects
require maintenance of physiological C-peptide
concentrations for a major proportion of the day.
Keywords: C-peptidenociceptive neuropathydiabetes mellitus