Hormonal regulation of ENaCs: insulin and aldosterone

Abstract

Although a variety of hormones and other agents modulate renal Na+ transport acting by way of the epithelial Na+ channel (ENaC), the mode(s), pathways, and their interrelationships in regulation of the channel remain largely unknown. It is likely that several hormones may be present concurrently in vivo, and it is, therefore, important to understand potential interactions among the various regulatory factors as they interact with the Na+transport pathway to effect modulation of Na+ reabsorption in distal tubules and other native tissues. This study represents specifically a determination of the interaction between two hormones, namely, aldosterone and insulin, which stimulate Na+ transport by entirely different mechanisms. We have used a noninvasive pulse protocol of blocker-induced noise analysis to determine changes in single-channel current ( i Na), channel open probability ( P o), and functional channel density ( N T) of amiloride-sensitive ENaCs at various time points following treatment with insulin for 3 h of unstimulated control and aldosterone-pretreated A6 epithelia. Independent of threefold differences of baseline values of transport caused by aldosterone, 20 nM insulin increased by threefold and within 10–30 min the density of the pool of apical membrane ENaCs ( N T) involved in transport. The very early (10 min) increases of channel density were accompanied by relatively small decreases of i Na(10–20%) and decreases of P o (28%) in the aldosterone-pretreated tissues but not the control unstimulated tissues. The early changes of i Na, P o, and N T were transient, returning very slowly over 3 h toward their respective control values at the time of addition of insulin. We conclude that aldosterone and insulin act independently to stimulate apical Na+ entry into the cells of A6 epithelia by increase of channel density.

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

“…The effects of aldosterone and insulin or IGF-1 may be additive [17]. Insulin stimulates SGK1 and is thus expected to enhance ENaC activity and renal Na + reabsorption [6][7][8]. SGK1 contributes to the regulation of renal Na + excretion by aldosterone, insulin, and IGF-1.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…One effect of insulin signaling in the gut is the upregulation of ENaC receptors and the increase of ENaC's permeability. 96 Reversetranscription polymerase chain reaction data have revealed that taste cells express the insulin receptor. 75 Furthermore, patch-clamp studies revealed that sodium þ influx increased significantly upon insulin administration in ENaC-responsive taste cells.…”

The number of K + channels in the plasma membrane of guard cell protoplasts changes in parallel with the surface area

“…Examples include the cAMP-induced insertion of the cystic fibrosis transmembrane conductance regulator (CFTR; ref. 3) and the promotion of delivery of epithelial Na ϩ channels to the apical membrane by aldosterone and insulin (4,5). Also, hypoosmotically induced swelling of renal epithelial cells was found to result in the insertion of Na ϩ channels into the plasma membrane (6).…”