Journal
DIABETES
Volume 56, Issue 12, Pages 2997-3005Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db07-0740
Keywords
-
Categories
Funding
- NCCIH NIH HHS [R01AT002146] Funding Source: Medline
- NIDDK NIH HHS [5P60 DK20572] Funding Source: Medline
- NINDS NIH HHS [NS047653-03] Funding Source: Medline
Ask authors/readers for more resources
OBJECTIVE-Activation of the cyclooxygenase (COX) pathway with secondary neurovascular deficits are implicated in the pathogenesis of experimental diabetic peripheral neuropathy (DPN). The aim of this study was to explore the interrelationships between hyperglycemia, activation of the COX-2 pathway, and oxidative stress and inflammation in mediating peripheral nerve dysfunction and whether COX-2 gene inactivation attenuates nerve fiber loss in long-term experimental diabetes. RESEARCH DESIGN AND METHODS-Motor and sensory digital nerve conduction velocities, sciatic nerve indexes of oxidative stress, prostaglandin content, markers of inflammation, and intraepidermal nerve fiber (IENF) density were measured after 6 months in control and diabetic COX-2-deficient (COX-2(-/-)) and littermate wild-type (COX-2(+/+)) mice. The effects of a selective COX-2 inhibitor, celecoxib, on these markers were also investigated in diabetic rats. RESULTS-Under normal conditions, there were no differences in blood glucose, peripheral nerve electrophysiology, markers of oxidative stress, inflammation, and IENF density between COX-2(+/+) and COX-2(-/-) mice. After 6 months, diabetic COX-2(+/+) mice experienced significant deterioration in nerve conduction velocities and IENF density and developed important signs of increased oxidative stress and inflammation compared with nondiabetic mice. Diabetic COX-2(-/-) mice were protected against functional and biochemical deficits of experimental DPN and against nerve fiber loss. In diabetic rats, selective COX-2 inhibition replicated this protection. CONCLUSIONS-These data suggest that selective COX-2 inhibition may be useful for preventing or delaying DPN.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available