{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:52:46Z","timestamp":1778939566734,"version":"3.51.4"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK039308"],"award-info":[{"award-number":["R01DK039308"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56DK116828"],"award-info":[{"award-number":["R56DK116828"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37HL023081"],"award-info":[{"award-number":["R37HL023081"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01HL074940"],"award-info":[{"award-number":["P01HL074940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL092196"],"award-info":[{"award-number":["R01HL092196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK119652"],"award-info":[{"award-number":["R01DK119652"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Overseas Research and Training Project of Talents of Henan Provincial Department of Health","award":["2018103"],"award-info":[{"award-number":["2018103"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22083951","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:04:06Z","timestamp":1618196646000},"page":"3951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NFAT5 Is Involved in GRP-Enhanced Secretion of GLP-1 by Sodium"],"prefix":"10.3390","volume":"22","author":[{"given":"Caini","family":"Fan","sequence":"first","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"},{"name":"Department of Hypertension, Henan Provincial People\u2019s Hospital, Zhengzhou University People\u2019s Hospital, Henan University People\u2019s Hospital, Zhengzhou 450003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laureano D.","family":"Asico","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Van Anthony M.","family":"Villar","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Hunt","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Cuevas","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Armando","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro A.","family":"Jose","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"},{"name":"Department of Physiology\/Pharmacology, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prasad R.","family":"Konkalmatt","sequence":"additional","affiliation":[{"name":"Division of Renal Diseases &amp; Hypertension, The George Washington University School of Medicine &amp; Health Science, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1056\/NEJMra1212606","article-title":"Salt in health and disease a delicate balance","volume":"368","author":"Kotchen","year":"2013","journal-title":"N. 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