Effect of streptozotocin-induced diabetes on rat liver Na+/K+-ATPase

Na+/K+-ATPase during diabetes may be regulated by synthesis of its alpha an d beta subunits and by changes in membrane fluidity and lipid composition. As these mechanisms were unknown in liver, we studied in rats the effect of streptozotocin-induced diabetes on liver Na+/K+-ATPase. We then evaluated whether fish oil treatment prevented the diabetes-induced changes. Diabetes mellitus induced an increased Na+/K+-ATPase activity and an enhanced expre ssion of the beta(1) subunit; there was no change in the amount of the alph a(1) and beta(3) isoenzymes. Biphasic ouabain inhibition curves were obtain ed for diabetic groups indicating the presence of low and high affinity sit es. No alpha(2 and) alpha(3) isoenzymes could be detected. Diabetes mellitu s led to a decrease in membrane fluidity and a change in membrane lipid com position. The diabetes-induced changes are not prevented by fish oil treatm ent. The results suggest that the increase of Na+/K+-ATPase activity can be associated with the enhanced expression of the beta(1) subunit in the diab etic state, but cannot be attributed to changes in membrane fluidity as typ ically this enzyme will increase in response to an enhancement of membrane fluidity. The presence of a high-affinity site for ouabain (IC50 = 10(-7) m ) could be explained by the presence of (alpha beta)(2) diprotomeric struct ure of Na+/K+-ATPase or an as yet unknown alpha subunit isoform that may ex ist in diabetes mellitus. These stimulations might be related, in part, to the modification of fatty acid content during diabetes.