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  • Title: Diabetes- and semi-starvation-induced changes in metabolism and regulation of Na,K-ATPase in rat heart.
    Author: Ziegelhöffer A, Bundgaard H, Ravingerová T, Tribulová N, Enevoldsen MT, Kjeldsen K.
    Journal: Diabetes Nutr Metab; 2003 Aug; 16(4):222-31. PubMed ID: 14768771.
    Abstract:
    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.
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