ALTERATIONS OF NA,K-ATPASE ISOENZYMES IN THE RAT DIABETIC NEUROPATHY - PROTECTIVE EFFECT OF DIETARY SUPPLEMENTATION WITH N-3 FATTY-ACIDS

Diabetic neuropathy is a degenerative complication of diabetes accompa nied by an alteration of nerve conduction velocity (NCV) and Na,K-ATPa se activity, The present study in rats was designed first to measure d iabetes-induced abnormalities in Na,K-ATPase activity, isoenzyme expre ssion, fatty acid content in sciatic nerve membranes, and NCV and seco nd to assess the preventive ability of a fish oil-rich diet (rich in n -3 fatty acids) on these abnormalities. Diabetes was induced by intrav enous streptozotocin injection. Diabetic animals (D) and nondiabetic c ontrol animals (C) were fed the standard rat chow either without suppl ementation or supplemented with either fish oil (DM, GM) or olive oil (DO, CO) at a daily dose of 0.5 g/kg by gavage during 8 weeks. Analysi s of the fatty acid composition of purified sciatic nerve membranes fr om diabetic animals showed a decreased incorporation of C16:l(n-7) fat ty acids and arachidonic acids. Fish oil supplementation changed the f atty acid content of sciatic nerve membranes, decreasing C18:2(n-6) fa tty acids and preventing the decreases of arachidonic acids and C18:1 (n-9) fatty acids. Protein expression of Na,K-ATPase a subunits, Na,K- ATPase activity, and ouabain affinity were assayed in purified sciatic nerve membranes from CO, DO, and DM, Na,K-ATPase activity was signifi cantly lower in sciatic nerve membranes of diabetic rats and significa ntly restored in diabetic animals that received fish oil supplementati on. Diabetes induced a specific decrease of alpha 1- and alpha 3-isofo rm activity and protein expression in sciatic nerve membranes. Fish oi l supplementation restored partial activity and expression to varying degrees depending on the isoenzyme. These effects were associated with a significant beneficial effect on NCV. This study indicates that fis h oil has beneficial effects on diabetes-induced alterations in sciati c nerve Na,K-ATPase activity and function.