ALTERATIONS IN THE PROPERTIES AND ISOFORM RATIOS OF BRAIN NA+/K+-ATPASE IN STREPTOZOTOCIN-DIABETIC RATS

In this study we analysed the changes in the properties of rat cerebral cortex Na+/K+-ATPase in streptozotocin induced diabetes (STZ-diabetes), Special attempt was made to determine whether insulin treatment of diabetic animals could restore the altered parameters of this enzyme. Na+/K+-ATPase activity was found to be decreased by 15% after 2 weeks, and by 37% after 4 weeks in diabetic rat brains with a parallel decrease in maximal capacity of low affinity ouabain binding sites. There was no significant change in the high affinity ouabain binding sites. The K-d values did not change significantly. Western blot analysis of brain Na+/K+-ATPase isoforms indicated a 61 +/- 5.8% and 20 +/- 2.8% decrease of the alpha(1) and alpha(3) isoforms, respectively in 4 weeks diabetic animals. Change in the amount of the alpha(2) isoform proved to be less characteristic, Both types of beta subunit isoform showed a significant decrease in four weeks diabetic rats. Our data indicate a good correlation in diabetic rats between changes in Na+/K+-ATPase activity, low affinity ouabain binding capacity and the level of alpha(1) isoform, While insulin treatment of diabetic animals restored the blood glucose level to normal, a complete reversal of diabetes induced changes in Na+/K+-ATPase activity, ouabain binding capacity and Na+/K+-ATPase isoform composition could not be achieved.