Alterations in levels of Na(+)-K(+)-ATPase isoforms in heart, skeletal muscle, and kidney of diabetic rats

Abstract

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)

Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats

“…The reduction in Na,K-ATPase activity was consistent with the results of a previous study using the same experimental model with a different enzymatic assay, i. e. measurement of K-stimulated pNPPase, which is a partial reaction of the Na,K-ATPase enzymatic cycle [9]. The observation of a decreased Mg-ATPase activity in native vesicles could be related to the sensitivity of enzyme activity to lipid environments.…”

“…The two isoenzymes appear to be specifically affected by these two parameters. Ng et al [9] studied changes caused by STZ-induced diabetes on expression of cardiac Na,K-ATPase subunit isoforms and reported that a 2 and b 1 protein expression decreased while a 1 protein expression remained unchanged. The Northern blot analysis confirms these results on protein expression.…”

Identification of differentially expressed genes in skeletal muscle of non-diabetic insulin-resistant and insulin-sensitive Pima Indians by differential display PCR

“…Several isoforms of Na + /K + -ATPase exist from different combinations of the α and β subunits [22]. In the streptozotocin (STZ) rat model of diabetes, increased muscle α2 subunit mRNA [23] and protein concentrations [24] with no change or decrease of enzyme activity were observed in skeletal muscle. The increase in α2 mRNA concentration was thought to be a compensatory increase due to the decreased Na + /K + -ATPase activity under hypoinsulinaemic state, which occurred in the STZ-induced diabetes or after 48-h fasting in rats [23].…”

Changes in the expression of Na+/K+-ATPase isoenzymes in the left ventricle of diabetic rat hearts: effect of insulin treatment

“…Recently, it has also been demonstrated that in the heart, streptozotocin-induced diabetes caused a conspicuous reduction in enzyme activity with a marked decrease of alpha 2 [13]. In an earlier study, Fawzi and McNeill [14] reported a decrease of both low and high affinity ouabain binding sites in left ventricle obtained from chronically diabetic rats.…”