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 accompanied by an alteration of nerve conduction velocity (NCV) and Na,K-ATPase activity. The present study in rats was designed first to measure diabetes-induced abnormalities in Na,K-ATPase activity, isoenzyme expression, fatty acid content in sciatic nerve membranes, and NCV and second to assess the preventive ability of a fish oil-rich diet (rich in n-3 fatty acids) on these abnormalities. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (D) and nondiabetic control animals (C) were fed the standard rat chow either without supplementation or supplemented with either fish oil (DM, CM) or olive oil (DO, CO) at a daily dose of 0.5 g/kg by gavage during 8 weeks. Analysis of the fatty acid composition of purified sciatic nerve membranes from diabetic animals showed a decreased incorporation of C16:1(n-7) fatty acids and arachidonic acids. Fish oil supplementation changed the fatty acid content of sciatic nerve membranes, decreasing C18:2(n-6) fatty acids and preventing the decreases of arachidonic acids and C18:1(n-9) fatty acids. Protein expression of Na,K-ATPase alpha 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 significantly lower in sciatic nerve membranes of diabetic rats and significantly restored in diabetic animals that received fish oil supplementation. Diabetes induced a specific decrease of alpha1- and alpha3-isoform activity and protein expression in sciatic nerve membranes. Fish oil 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 fish oil has beneficial effects on diabetes-induced alterations in sciatic nerve Na,K-ATPase activity and function.
Division of Diabetology, CHU Timone, School of Medicine, I.F.R. Jean Roche, Marseille, France.
A
A
Gerbi
J M
JM
Maixent
O
O
Barbey
I
I
Jamme
M
M
Pierlovisi
T
T
Coste
G
G
Pieroni
A
A
Nouvelot
P
P
Vague
D
D
Raccah
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D003929:Diabetic Neuropathies / Q000178:diet therapy* / Q000201:enzymology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D000069463:Olive Oil; D010042:Ouabain / Q000494:pharmacology; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology
D004042:Dietary Fats, Unsaturated; D004791:Enzyme Inhibitors; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007527:Isoenzymes; D000069463:Olive Oil; D010938:Plant Oils; D016718:Arachidonic Acid; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase