Beneficial effects of gamma linolenic acid supplementation on nerve conduction velocity, Na+, K+ ATPase activity, and membrane fatty acid compositionin sciatic nerve of diabetic rats

Metabolic and vascular abnormalities are implicated in the pathogenesis of diabetic neuropathy. Two principal metabolic defects are altered lipid meta bolism 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 enz yme maintains the membrane electrical potential and allows repolarization, disturbances in its activity can alter the process of nerve conduction velo city (NCV). We studied the effects of supplementation with GLA (260 mg per day) on NCV, fatty acid phospholipid composition, and Na+, K+ ATPase activi ty 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 wi th no supplementation and 12 weeks supplemented with sunflower oil. To test the ability of GLA to prevent or reverse the effects of diabetes, two grou ps 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+ A TPase activity (P < 0.0001), and an abnormal phospholipid fatty acid compos ition. GLA restored NCV both in the prevention and reversal studies and par tially restored Na+, K+ ATPase activity in the preventive treatment group ( P < 0.0001). These effects were accompanied by ct modification of phospholi pid fatty acid composition in nerve membranes. Overall, the results suggest that membrane fatty acid composition plays a direct role in NCV and confir m the beneficial effect of GLA supplementation in diabetic neuropathy. (C) Elsevier Science Inc. 1999. All rights reserved.