Diabetes- and semi-starvation-induced changes in metabolism and regulation of Na,K-ATPase in rat heart.
OBJECTIVE
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
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.
Ziegelhöffer
A
A
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia.
Bundgaard
H
H
Ravingerová
T
T
Tribulová
N
N
Enevoldsen
M T
MT
Kjeldsen
K
K
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013217:Starvation / Q000201:enzymology*; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
D001786:Blood Glucose; D002118:Calcium; D000252:Calcium-Transporting ATPases; D002784:Cholesterol; D006442:Glycated Hemoglobin; D011188:Potassium; D000254:Sodium-Potassium-Exchanging ATPase; D014280:Triglycerides