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 alpha 2-levels, a moderate decrease in beta 1-levels, and no significant change in alpha 1-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 alpha 1- and alpha 2-levels in skeletal muscle and in alpha 1- and beta 1-levels in kidneys of diabetic rats. There was also a detectable, but not significant, increase in beta 1-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 days of insulin treatment (10 U/kg sc) partially reversed the decreased alpha 2- and beta 1-levels in diabetic cardiac muscle, without significant effect on alpha 1-levels. In skeletal muscle, insulin treatment also partially reversed the elevated alpha 1- and alpha 2-levels but was without significant effect on beta 1-levels. It is concluded that STZ-induced diabetes exerted isoform- and tissue-specific regulation of the Na(+)-K(+)-ATPase subunit isoforms.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Pharmacology, College of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
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D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D007527:Isoenzymes; D000254:Sodium-Potassium-Exchanging ATPase