Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Western Kentucky University, Bowling Green, KY, 42101, USA.
Sci Rep. 2019 Mar 12;9(1):4296. doi: 10.1038/s41598-019-40639-x.
Recent studies have suggested that postprandial increases in insulin directly contribute to reduced urinary sodium excretion. An abundance of research supports the ability of insulin to augment epithelial sodium channel (ENaC) transport. This study hypothesized that ENaC contributes to the increase in renal sodium reabsorption following a meal. To test this, we used fasted or 4 hour postprandial Sprague Dawley rats to analyze ENaC expression and activity. We also assessed total expression of additional sodium transporters (Na-Cl cotransporter (NCC), Na-K-2Cl cotransporter (NKCC2), and Na-K-ATPase (NKA)) and circulating hormones involved in the renin-angiotensin-aldosterone system (RAAS). We found that after carbohydrate stimulus, ENaC open probability increased in split-open isolated collecting duct tubules, while ENaC protein levels remained unchanged. This was supported by a lack of change in phosphorylated Nedd4-2, an E3 ubiquitin ligase protein which regulates the number of ENaCs at the plasma membrane. Additionally, we found no differences in total expression of NCC, NKCC2, or NKA in the postprandial rats. Lastly, there were no significant changes in RAAS signaling between the stimulated and fasted rats, suggesting that acute hyperinsulinemia increases ENaC activity independent of the RAAS signaling cascade. These results demonstrate that insulin regulation of ENaC is a potential mechanism to preserve sodium and volume loss following a meal, and that this regulation is distinct from classical ENaC regulation by RAAS.
最近的研究表明，胰岛素餐后增加直接导致尿钠排泄减少。大量研究支持胰岛素增强上皮钠通道（ENaC）转运的能力。本研究假设 ENaC 有助于餐后肾脏钠重吸收的增加。为了验证这一点，我们使用禁食或餐后 4 小时的 Sprague Dawley 大鼠来分析 ENaC 的表达和活性。我们还评估了其他钠转运体（Na-Cl 共转运体（NCC）、Na-K-2Cl 共转运体（NKCC2）和 Na-K-ATP 酶（NKA））的总表达以及参与肾素-血管紧张素-醛固酮系统（RAAS）的循环激素。我们发现，在碳水化合物刺激后，分离的集合管小管中 ENaC 的开放概率增加，而 ENaC 蛋白水平保持不变。这得到了缺乏变化的支持，磷酸化 Nedd4-2 是一种 E3 泛素连接酶蛋白，调节质膜上的 ENaC 数量。此外，我们发现餐后大鼠的 NCC、NKCC2 或 NKA 的总表达没有差异。最后，刺激和禁食大鼠之间的 RAAS 信号没有显著变化，表明急性高胰岛素血症增加 ENaC 活性独立于 RAAS 信号级联。这些结果表明，胰岛素对 ENaC 的调节是餐后保留钠和容量丢失的潜在机制，并且这种调节与 RAAS 对 ENaC 的经典调节不同。
