Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic
neuropathy. Two principal metabolic defects are altered lipid metabolism resulting
from the impairment of delta-6-desaturase, which converts linoleic acid (LA) into
gamma linolenic acid (GLA), and reduced nerve Na+, K+ ATPase activity. This reduction
may be caused by a lack of incorporation of (n-6) fatty acids in membrane phospholipids.
Because this ubiquitous enzyme maintains the membrane electrical potential and allows
repolarization, disturbances in its activity can alter the process of nerve conduction
velocity (NCV). We studied the effects of supplementation with GLA (260 mg per day)
on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activity in streptozotocin-diabetic
rats. Six groups of 10 rats were studied. Two groups served as controls supplemented
with GLA or sunflower oil (GLA free). Two groups with different durations of diabetes
were studied: 6 weeks with no supplementation and 12 weeks supplemented with sunflower
oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two
groups of diabetic rats were supplemented with GLA, one group for 12 weeks and one
group for 6 weeks, starting 6 weeks after diabetes induction. Diabetes resulted in
a 25% decrease in NCV (P < 0.0001), a 45% decrease in Na+, K+ ATPase activity (P <
0.0001), and an abnormal phospholipid fatty acid composition. GLA restored NCV both
in the prevention and reversal studies and partially restored Na+, K+ ATPase activity
in the preventive treatment group (P < 0.0001). These effects were accompanied by
a modification of phospholipid fatty acid composition in nerve membranes. Overall,
the results suggest that membrane fatty acid composition plays a direct role in NCV
and confirm the beneficial effect of GLA supplementation in diabetic neuropathy.