Extracellular fluid volume expansion uncovers a natriuretic action of GLP-1: a functional GLP-1-renal axis in man

Ali Asmar, Per K Cramon, Lene Simonsen, Meena Asmar, Charlotte M Sorensen, Sten Madsbad, Cedric Moro, Bolette Hartmann, Boye L Jensen, Jens Juul Holst, Jens Bülow

29 Citations (Scopus)


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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Issue number7
Pages (from-to)2509-2519
Number of pages11
Publication statusPublished - 1 Jul 2019


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