Alterations of Na,K‐ATPase Isoenzymes in the Rat Diabetic Neuropathy: Protective Effect of Dietary Supplementation with n‐3 Fatty Acids

Abstract

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 NOV 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 (0) were fed the standard rat chow either without supplementation or supplemented with either fish oil (DM, CM) or olive oil (DO, 00) 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 Cl 6:1 (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 018:1 (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 00, 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 aland a3-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 NOV. This study indicates that fish oil has beneficial effects on diabetes-induced alterations in sciatic nerve Na,K-ATPase activity and function.

ACE inhibition salvages the visual loss caused by diabetes

“…Hence, Na + -K + ATPase activity is central to phototransduction and any perturbation in its activity will manifest as an altered phototransduction amplitude [28]. It is noteworthy that in diabetes, reduced Na + -K + ATPase activity is observed in a variety of different cell types [29], including those of the retina [16].…”

“…Abnormal expression of Na + -K + ATPase subunits has been reported in the cardiac muscle membranes of diabetic animals [29], although a change in expression does not seem to occur in the retina [16]. Nevertheless, it is established that the renin-angiotensin system (RAS) and, in particular, that angiotensin-II (AngII), can modulate Na + -K + ATPase activity [30].…”

Neutral Phospholipids Stimulate Na,K-ATPase Activity

“…lateral pressure) of the polyunsaturated fatty acyl phospholipids within the lipid bilayer (46). In other studies dietary modulation of the -6:-3 fatty acyl ratio in heart or brain phospholipids has also been reported to alter kinetic properties of the different Na,K-ATPase isoforms (47)(48)(49). Although it is quite possible that kinetic effects are mediated by changes in the physical environment of the Na,K-ATPase, as suggested in these papers, in an intact membrane or reconstituted proteoliposomes the exact mechanism of effects of phospholipids on activity is not easily defined.…”

n-3 Fatty Acids in the Treatment of Diabetic Patients

“…While mechanisms responsible for an impairment of Na,K-ATPase during hyperglycemia remain to be elucidated, it has been suggested that alterations in membrane fatty acid composition, particularly related to a deficiency in DHA, might explain the abnormal Na ϩ transport observed in these patients (138,139). Djemli-Shipkolye et al (140) have demonstrated that fish oil supplementation can modify the fatty acid composition of sciatic nerve membranes of diabetic rats by decreasing LA and preventing the decrease of arachidonic and oleic acid.…”