ALTERATIONS IN LEVELS OF NA+-K+-ATPASE ISOFORMS IN HEART, SKELETAL-MUSCLE, AND KIDNEY OF DIABETIC RATS

In streptozotocin (STZ)-induced diabetic rats, activities of Na+-K+-ATPase and the Na pump have been shown to be altered. Cellular mechanisms underlying such changes remain unclear. The present studies examined by immunoblotting the levels of Na+-K+-ATPase subunit isoforms in heart, skeletal muscle, and kidney of diabetic rats. Effects of insulin treatment on these levels were also studied. In cardiac muscle, STZ-induced diabetes caused a marked decrease in alpha2-levels, a moderate decrease in beta1-levels, and no significant change in alpha1-levels. Corresponding to these changes, Na+-K+-ATPase activity, estimated by K+-dependent p-nitrophenylphosphatase activity, also decreased. By contrast, there were significant increases in alpha1- and alpha2-levels in skeletal muscle and in alpha1- and beta1-levels in kidneys of diabetic rats. There was also a detectable, but not significant, increase in beta1-levels in diabetic skeletal muscle. In kidney, the increase in subunit levels was associated with significantly increased Na+-K+-ATPase activity, whereas, in skeletal muscle, no increase in enzyme activity was observed. In diabetic rats, 7 clays of insulin treatment (10 U/kg sc) partially reversed the decreased alpha2- and beta1-levels in diabetic cardiac muscle, without significant effect on alpha1-levels. In skeletal muscle, insulin treatment also partially reversed the elevated alpha1- and alpha2-levels but was without significant effect on beta1-levels. It is concluded that STZ-induced diabetes exerted isoform- and tissue-specific regulation of the Na+-K+-ATPase subunit isoforms. Furthermore, insulin treatment reversed, in varying degrees, some of these alterations, despite persistent presence of hyperglycemia.