Diabetes- and semi-starvation-induced changes in metabolism and regulation of Na, K-ATPase in rat heart

Aims/hypothesis: In comparison with healthy controls, rats with streptozotocin-induced diabetes exhibit retarded gain in body weight. This is generally attributed to lowered protein synthesis resulting from abnormal metabolism. Furthermore, decreased abundance and activity of Na,K-ATPase in heart and skeletal muscle has been described. However, decreased gain in body weight per se is accompanied by a down-regulation of skeletal muscle Na,K-ATPase. Thus, the aim of the present study was to evaluate cardiac Na,K-ATPase in semi-starvation and diabetes. Methods: Diabetes was induced in male Wistar rats with streptozotocin. In healthy parallel running control rats body weight gain was kept reduced by limited food intake. Results: Semi-starved and diabetic rats demonstrated 18 and 16% (p<0.05) retarded gain in body weight after 63 days. As compared to semi-starved rats, diabetic animals exhibited a 59-273% (p<0.05) increase in glucose, glycohaemoglobin, triglyceride and cholesterol plasma levels. Activity of heart K-pNPPase, reflecting Na,K-ATPase, in crude membrane homogenates was reduced by 29 and 10% (p<0.05) by diabetes and semi-starvation. The age-dependent reduction in heart K-pNPPase in normal controls was 6%. After subtracting the age-dependent change, the reductions were 25 and 4% in diabetes and semi-starvation, respectively. After subtracting the semi-starvation-associated change, the diabetes-induced reduction was 22-27%. The reduction was in accord with measurements of Na,K-ATPase activities in partially purified membranes, Na,K-ATPase isoforms and cytochemical evaluations. Expressed per heart, the reduction in Na,K-ATPase was 30%. Conclusions/interpretation: Streptozotocin-induced diabetes selectively reduces heart Na,K-ATPase concentration by around 1/4, which reduces the capacity of the heart for maintaining K- and Ca-homeostasis. This may pose a risk of arrhythmias and may be associated with heart failure in diabetic cardiomyopathy.