Abstract
Gastrin, secreted by G-cells, and glucagon-like peptide-1 (GLP-1), secreted by L-cells, may participate in the regulation of sodium balance. We studied the effect of sodium in mice in vivo and mouse ileum and human L-cells, on GLP-1 secretion, and the role of NFAT5 and gastrin-releasing peptide receptor (GRPR) in this process. A high-sodium diet increases serum GLP-1 levels in mice. Increasing sodium concentration stimulates GLP-1 secretion from mouse ileum and L-cells. GRP enhances the high sodium-induced increase in GLP-1 secretion. High sodium increases cellular GLP-1 expression, while low and high sodium concentrations increase NFAT5 and GRPR expression. Silencing NFAT5 in L-cells abrogates the stimulatory effect of GRP on the high sodium-induced GLP-1 secretion and protein expression, and the sodium-induced increase in GRPR expression. GLP-1 and gastrin decrease the expression of Na+-K+/ATPase and increase the phosphorylation of sodium/hydrogen exchanger type 3 (NHE3) in human renal proximal tubule cells (hRPTCs). This study gives a new perspective on the mechanisms of GLP-1 secretion, especially that engendered by ingested sodium, and the ability of GLP-1, with gastrin, to decrease Na+-K+/ATPase expression and NHE3 function in hRPTCs. These results may contribute to the better utilization of current and future GLP-1-based drugs in the treatment of hypertension.
Highlights
glucagon-like peptide-1 (GLP-1) levels were highest in mice gavaged with high salt (HS), followed by mice gavaged with normal salt (NS), and least in mice gavaged with low salt (LS) (p < 0.05)
GLP-1 levels at 1 h after gavage remained higher than before gavage in the NS and HS groups. These results show that GLP-1 secretion into the blood is influenced by the sodium content of food and suggests that GLP-1 may be an effector enterokine that responds to an increase in sodium intake
NFAT5 expression in L-cells can be stimulated by high sodium concentration
Summary
Increased sodium intake is one of the most important factors in the pathogenesis of hypertension. After a high sodium diet intake, the body excretes the excess sodium through a variety of mechanisms to maintain sodium and fluid balance and keep the blood pressure in the normal range [1]. In salt-sensitive states, a high sodium intake results in sodium accumulation in the body due to impaired renal sodium excretion, related to the failure of pressure-natriuresis and compensatory neural and hormonal mechanisms; the blood pressure increases. In salt-resistant states, sodium is excreted efficiently to maintain the blood pressure in the normal range [2]. The gastrointestinal-renal axis plays an important role in the regulation of fluid and electrolyte balance and blood pressure [3,4,5]. Sensing the amount of ingested sodium by the gastrointestinal tract (GIT)
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