Remote neurotrophic support of epidermal nerve fibres in experimental diabetes.
OBJECTIVE
The support of distal regenerating axons and epidermal nerve fibres through growth factor delivery may depend on the site of delivery. While low-dose systemic insulin provides trophic support for regenerating axons or axons from diabetic animals, its potential action upon the most distal neurites within the epidermis is unknown. In diabetic neuropathy, distal loss of axons is an important clinical and pathological feature. We hypothesised that insulin and IGF-1 delivered intrathecally could support the most distal epidermal nerve fibres.


METHODS
As insulin and IGF-1 receptors are present upon sensory ganglion perikarya, we studied the impact of intrathecal delivery of low-dose insulin and equimolar IGF-1 on the density of epidermal axons expressing protein gene product 9.5 in experimental diabetic rats. After 2 months of diabetes induced by streptozotocin injection, intrathecal delivery of low-dose insulin or IGF-1 or saline was provided for 1 month, with comparison to compatible doses of subcutaneous insulin delivery.


RESULTS
Diabetes, in itself, was associated with a decline in epidermal nerve fibre density. Delivery of both intrathecal IGF-1 and insulin was associated with significant improvement in epidermal fibre density (greatest with IGF-1) and length relative to placebo.


CONCLUSIONS
Central intrathecal delivery of IGF-1 and insulin offers remote support for epidermal nerve fibres, subjected to 'dying-back' in early diabetic polyneuropathy.
Toth
C
C
Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. corytoth@shaw.ca
Brussee
V
V
Zochodne
D W
DW
D000818:Animals; D001369:Axons / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D002408:Catheters, Indwelling; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D007263:Infusions, Parenteral; D007278:Injections, Spinal; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation*
D001786:Blood Glucose; D002951:Citrates; D007328:Insulin