Extracellular Fluid Volume Expansion Uncovers a Natriuretic Action of GLP-1: A Functional GLP-1–Renal Axis in Man

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 7; pp. 2509 - 2519
• Main Authors: Asmar, Ali, Cramon, Per K, Simonsen, Lene, Asmar, Meena, Sorensen, Charlotte M, Madsbad, Sten, Moro, Cedric, Hartmann, Bolette, Jensen, Boye L, Holst, Jens J, Bülow, Jens
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.07.2019; Copyright Oxford University Press; Oxford University Press
• Subjects: Adult; Angiotensin; Angiotensin II; Diabetes mellitus (non-insulin dependent); Drinking - physiology; Ethylenediaminetetraacetic acid; Glomerular filtration rate; Glomerular Filtration Rate - physiology; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - metabolism; Healthy Volunteers; Hemodynamics; Humans; Infusions, Intravenous; Intravenous administration; Kidney Tubules - physiology; Kidneys; Male; Medical equipment and supplies industry; Medical test kit industry; Natriuresis - physiology; Renal function; Renal Plasma Flow - physiology; Renin; Sodium; Sodium chloride; Type 2 diabetes; Young Adult; Denmark; United States
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2019-00004

Abstract Purpose We have previously demonstrated that glucagon-like peptide-1 (GLP-1) does not affect renal hemodynamics or function under baseline conditions in healthy participants and in patients with type 2 diabetes mellitus. However, it is possible that GLP-1 promotes natriuresis under conditions with addition of salt and water to the extracellular fluid. The current study was designed to investigate a possible GLP-1–renal axis, inducing natriuresis in healthy, volume-loaded participants. Methods Under fixed sodium intake, eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Timed urine collections were conducted throughout the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake and release of hormones and ions were measured via Fick’s principle. Results During GLP-1 infusion, urinary sodium and osmolar excretions increased significantly compared with vehicle. Plasma renin levels decreased similarly on both days, whereas angiotensin II (ANG II) levels decreased significantly only during GLP-1 infusion. RPF and GFR remained unchanged on both days. Conclusions In volume-loaded participants, GLP-1 induces natriuresis, probably brought about via a tubular mechanism secondary to suppression of ANG II, independent of renal hemodynamics, supporting the existence of a GLP-1–renal axis. The current study supports the existence of a GLP-1–mediated gut-renal axis for urinary sodium excretion in healthy participants as a mechanism contributing to extracellular volume regulation.