Na+/Mg2+ exchange is functionally coupled to the insulin receptor
Na+/Mg2+ exchange is functionally coupled to the insulin receptor
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DOI：
10.1002/jcp.10463
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发表时间：
2004-06-01
影响因子：
5.6
通讯作者：
Romero, JR
中科院分区：
文献类型：
--
作者：
Ferreira, A;Rivera, A;Romero, JR
Regulation of cellular Mg2+ levels by insulin has been shown in various tissues. However, the mechanisms for hormonal regulation of cellular Mg2+ have not been well described. We studied the effect of insulin on Na+/Mg2+ exchange in normal human cells, measuring Na+/Mg2+ exchange activity as net total Mg2+ efflux driven by an inward Na+ gradient in Mg2+-loaded red blood cells (RBCs). Na+/Mg2+ exchange was increased significantly by the addition of 2.4 nmol/L of insulin to the flux medium (from 0.60 +/- 0.06 mmol/L cell x h to 0.75 +/- 0.08 mmol/L cell x h [P-0.0098, n-44]). A dose-response curve for the effects of insulin on the exchanger activity gave an estimated EC50 for insulin of 0.95 +/- 0.31 nmol/L and a V-max of 0.86 +/- 0.12 mmol/L cell x h (n = 7). Kinetics of the Na+/Mg2+ exchange were characterized by measuring its activity as a function of Mg2+ and Na+ concentrations. The K-0.5 for cellular Mg2+ was not affected by incubation with insulin. However, the K-0.5 for extracellular Na+ decreased from 69.9 +/- 6.3 to 40.3 +/- 8.4 mol/L (n=5, P=0.03) in the presence of insulin. We also studied the effect of wortmannin (WT), a PI 3-kinase inhibitor, on activity of the exchanger. WT significantly blocked the insulin-stimulated Na+/Mg2+ activity (n=6, P= 0.048), with an IC50 of 0.5 nmol/L. LY294002, another PI 3-kinase inhibitor, likewise blocked the insulin-stimulated activity of the exchanger. Therefore, insulin regulates cellular Mg2+ metabolism in part via an increase in the affinity for Na+ of the Na+/Mg2+ exchange and PI 3-kinase activation, suggesting another role for the PI 3-kinase pathway in insulin-mediated cellular events. J. Cell. Physiol. 199: 434-440, 2004. (C) 2003 Wiley-Liss, Inc.
