糖尿病和半饥饿诱导的大鼠心脏代谢变化及钠钾ATP酶的调节

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

作者信息

Ziegelhöffer A, Bundgaard H, Ravingerová T, Tribulová N, Enevoldsen M T, Kjeldsen K

机构信息

Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovakia.

出版信息

Diabetes Nutr Metab. 2003 Aug;16(4):222-31.

PMID: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.

摘要

目的/假设：与健康对照组相比，链脲佐菌素诱导的糖尿病大鼠体重增加迟缓。这通常归因于异常代谢导致蛋白质合成降低。此外，已有研究描述了心脏和骨骼肌中钠钾ATP酶的丰度和活性降低。然而，体重增加本身的减少伴随着骨骼肌钠钾ATP酶的下调。因此，本研究的目的是评估半饥饿和糖尿病状态下的心脏钠钾ATP酶。

方法

用链脲佐菌素诱导雄性Wistar大鼠患糖尿病。在健康的平行对照大鼠中，通过限制食物摄入量使体重增加减少。

结果

63天后，半饥饿和糖尿病大鼠的体重增加分别迟缓了18%和16%（p<0.05）。与半饥饿大鼠相比，糖尿病动物的血糖、糖化血红蛋白、甘油三酯和胆固醇血浆水平升高了59 - 273%（p<0.05）。反映钠钾ATP酶的心脏K-pNPPase在粗膜匀浆中的活性，因糖尿病和半饥饿分别降低了29%和10%（p<0.05）。正常对照组中，心脏K-pNPPase随年龄的降低为6%。减去年龄相关变化后，糖尿病和半饥饿状态下的降低分别为25%和4%。减去与半饥饿相关的变化后，糖尿病诱导的降低为22 - 27%。这种降低与部分纯化膜中钠钾ATP酶活性、钠钾ATP酶同工型的测量以及细胞化学评估结果一致。以心脏为单位计算，钠钾ATP酶的降低为30%。

结论/解读：链脲佐菌素诱导的糖尿病选择性地使心脏钠钾ATP酶浓度降低约1/4，这降低了心脏维持钾和钙稳态的能力。这可能会带来心律失常的风险，并且可能与糖尿病性心肌病中的心力衰竭有关。