Defective response to cAMP-dependent protein kinase in non-insulin-dependent diabetic heart.
Defective response to cAMP-dependent protein kinase in non-insulin-dependent diabetic heart.
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非胰岛素依赖性糖尿病心脏对 cAMP 依赖性蛋白激酶的反应缺陷。
DOI：
10.1152/ajpendo.1991.261.3.e369
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
White,T
中科院分区：
文献类型：
--
作者：
Schaffer,SW;Allo,S;Punna,S;White,T
从一岁大的非胰岛素依赖型糖尿病大鼠分离的心脏对β-肾上腺素能激动剂异丙肾上腺素的反应性降低。在3×10~(-9)~10~(-7)M的浓度范围内，异丙肾上腺素对糖尿病心脏左室压下降速率和左室压升高速率的刺激作用显著降低。为了阐明这一缺陷的基础，研究了参与β-肾上腺素能激动剂作用的各个步骤。二氢阿普洛尔结合实验显示，糖尿病患者的β-肾上腺素能受体数目和结合亲和力均未受到影响。糖尿病也不影响异丙肾上腺素对腺苷环化酶活性的刺激，心肌细胞3‘，5’-环磷酸腺苷(CAMP)的积聚，或cAMP依赖的蛋白激酶活性比率的增加。然而，研究发现，在存在和不存在cAMP依赖的蛋白激酶的情况下，糖尿病心脏的肌膜钙转运体的活性都显著受到抑制。蛋白激酶诱导的肌浆网钙转运的增强也被减弱。讨论了这些异常导致钙稳态和心肌收缩功能改变的可能性。
Hearts isolated from 1-yr-old non-insulin-dependent diabetic rats exhibited reduced responsiveness to the beta-adrenergic agonist isoproterenol. Over a concentration range of 3 x 10(-9) to 10(-7) M, isoproterenol-mediated stimulation in the rate of left ventricular pressure decline, a measure of myocardial relaxation, and the rate of left ventricular pressure rise, a measure of myocardial contractility, were significantly depressed in the diabetic hearts. To clarify the basis for this defect, individual steps involved in the actions of the beta-adrenergic agonists were examined. Dihydroalprenolol binding assays revealed that neither beta-adrenergic receptor number nor binding affinity was affected by the diabetic condition. Also unaffected by diabetes was isoproterenol-mediated stimulation of adenylate cyclase activity, myocyte accumulation of adenosine 3',5'-cyclic monophosphate (cAMP), or the increase in cAMP-dependent protein kinase activity ratio. However, it was found that both in the presence and absence of cAMP-dependent protein kinase, activity of the sarcolemmal calcium transporter was significantly depressed in the diabetic heart. Also attenuated was protein kinase-induced enhancement of sarcoplasmic reticular calcium transport. The likelihood that these abnormalities contribute to alterations in calcium homeostasis and myocardial contractile function is discussed.