Insulin activates Na+/H+ exchanger 3:: biphasic response and glucocorticoid dependence
Insulin activates Na+/H+ exchanger 3:: biphasic response and glucocorticoid dependence
复制标题
DOI：
10.1152/ajprenal.00365.2001
复制
发表时间：
2002-09-01
影响因子：
4.2
通讯作者：
Amb端hl, PM
中科院分区：
文献类型：
--
作者：
Klisic, J;Hu, MC;Amb端hl, PM
首次发表于3月26日，胰岛素是肾脏盐和水排泄的重要调节剂，高胰岛素血症与高血压有关。肾脏中胰岛素作用的靶蛋白之一是Na+/H+交换器3（NHE 3），其是负责哺乳动物近端小管中盐吸收的主要Na+转运蛋白。迄今为止，尚未研究胰岛素激活NHE 3的分子机制。在负鼠肾（OK）细胞中，胰岛素以时间和浓度依赖性方式增加Na+/H+交换活性。这种效应是由于NHE 3的激活，因为它在NHE 1和NHE 2的药理学抑制后持续存在。在刺激的早期阶段（2-12 h），NHE 3活性增加，而NHE 3蛋白和mRNA没有变化。在24小时，增强的NHE 3活性伴随着总的和细胞表面的NHE 3蛋白和NHE 3 mRNA丰度的增加。胰岛素对NHE 3活性、蛋白质和mRNA的所有影响在氢化可的松存在下被放大。这些结果表明，胰岛素刺激肾小管NHE 3活性通过一个双相机制，涉及翻译后因子和NHE 3基因表达的增加和效果是依赖于氢化可的松的许可行动。
First published March 26, Insulin is an important regulator of renal salt and water excretion, and hyperinsulinemia has been implicated to play a role in hypertension. One of the target proteins of insulin action in the kidney is Na+/H+ exchanger 3 (NHE3), a principal Na+ transporter responsible for salt absorption in the mammalian proximal tubule. The molecular mechanisms involved in activation of NHE3 by insulin have not been studied so far. In opossum kidney (OK) cells, insulin increased Na+/H+ exchange activity in a time- and concentration-dependent manner. This effect is due to activation of NHE3 as it persisted after pharmacological inhibition of NHE1 and NHE2. In the early phase of stimulation (2-12 h), NHE3 activity was increased without changes in NHE3 protein and mRNA. At 24 h, enhanced NHE3 activity was accompanied by an increase in total and cell surface NHE3 protein and NHE3 mRNA abundance. All the effects of insulin on NHE3 activity, protein, and mRNA were amplified in the presence of hydrocortisone. These results suggest that insulin stimulates renal tubular NHE3 activity via a biphasic mechanism involving posttranslational factors and an increase in NHE3 gene expression and the effects are dependent on the permissive action of hydrocortisone.