Sodium-lithium countertransport has low affinity for sodium in hyperinsulinemic hypertensive subjects.
Sodium-lithium countertransport has low affinity for sodium in hyperinsulinemic hypertensive subjects.
复制标题
在高胰岛素血症高血压受试者中，钠-锂逆向转运对钠的亲和力较低。
DOI：
10.1161/01.hyp.25.5.986
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Semplicini,A
中科院分区：
文献类型：
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作者：
Zerbini,G;Ceolotto,G;Gaboury,C;Mos,L;Pessina,AC;Canessa,M;Semplicini,A
我们最近报道，红细胞与胰岛素孵育显著降低了对外部Na+的亲和力，并增加了Na+-Li+逆向转运的最大转运速率（Vmax）。高血压与胰岛素抵抗及其代偿性高胰岛素血症的关联使我们研究了体内胰岛素水平与这种反向转运蛋白的Na+激活动力学之间的关系。我们研究了血压正常（n=28）和高血压（n=25）受试者禁食过夜后的血糖和胰岛素浓度。高血压受试者的胰岛素水平（11.7±1.5 μU/mL，平均值±SEM）高于血压正常受试者（8.2±1.2 μU/mL），但血糖水平相似，均在正常范围内。通过一种新的程序，使用等渗条件将外部Na+升高至280 mmol/L，以钠刺激的Li+流出量测量反向转运蛋白活性。在正常血压受试者中，Vmax在50和100 mmol/L Na+之间达到，而在大多数高血压受试者中，Na+浓度需要高于150 mmol/L。这种不同的动力学行为是因为高血压受试者的半最大激活（Km）的Na+浓度（58.9±5.3 mmol/L）是正常血压受试者（29.8±2.6 mmol/L，P<0.001）的两倍。空腹胰岛素水平大于10 μU/mL的高血压受试者（n=12）的Na+ Km高于胰岛素水平小于10 μU/mL的受试者（n=13）（分别为73.4±8.7和45.6±3.9 mmol/L，P<0.01），Vmax相似（分别为0.57±0.05和0.41±0.05 mmol · L-1· h-1）。相反，胰岛素水平大于10 μU/mL的正常血压受试者（n=6）的Vmax和Km值与胰岛素水平小于10 μU/mL的受试者（n=22）相似。简单回归分析表明，体重指数，胰岛素和血压与这两个动力学参数。多元逐步回归分析显示，Vmax主要受血压影响，Km主要受血压和胰岛素水平影响。低亲和力的Na+与体内高胰岛素血症及其伴随的高血压受试者中观察到的胰岛素抵抗的协会同意在体外胰岛素对这种反向转运蛋白的影响。
We recently reported that incubation of red blood cells with insulin markedly decreases the affinity for external Na+and increases the maximal transport rate (Vmax) of Na+-Li+countertransport. The association of hypertension with insulin resistance and its compensatory hyperinsulinemia led us to investigate the relationship between insulin levels in vivo and the Na+activation kinetics of this antiporter. We studied normotensive (n=28) and hypertensive (n=25) subjects after they had fasted overnight and determined their plasma glucose and insulin concentrations. Insulin levels were higher in the hypertensive subjects (11.7±1.5 μU/mL, mean±SEM) than in the normotensive subjects (8.2±1.2 μU/mL), but glucose levels were similar and within normal limits. Antiporter activity was measured as sodium-stimulated Li+efflux by a new procedure that uses isosmotic conditions to raise external Na+to 280 mmol/L. In normotensive subjects,Vmaxwas reached between 50 and 100 mmol/L Na+, whereas in most hypertensive subjects, Na+concentrations higher than 150 mmol/L were needed. This different kinetic behavior was because the Na+concentration for half-maximal activation (Km) was twofold higher in hypertensive subjects (58.9±5.3 mmol/L) than in normotensive subjects (29.8±2.6 mmol/L,P<.001). Hypertensive subjects with fasting insulin levels greater than 10 μU/mL (n=12) had a higherKmfor Na+than subjects with insulin levels less than 10 μU/mL (n=13) (73.4±8.7 versus 45.6±3.9 mmol/L, respectively,P<.01) and similarVmax(0.57±0.05 versus 0.41±0.05 mmol · L−1· h−1). In contrast, normotensive subjects with insulin levels greater than 10 μU/mL (n=6) hadVmaxandKmvalues similar to those with insulin levels less than 10 μU/mL (n=22). Simple regression analysis showed that body mass index, insulin, and blood pressure correlated with both kinetic parameters. However, stepwise multiple regression analysis showed that the main determinant ofVmaxwas blood pressure and forKm, blood pressure and insulin levels. The association of a low affinity for Na+with in vivo hyperinsulinemia and its concomitant insulin resistance observed in hypertensive subjects agrees with the in vitro effects of insulin on this antiporter.