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

PURPOSE: We have previously demonstrated that glucagon-like peptide (GLP)-1, does not affect renal hemodynamics or function under baseline conditions in healthy individuals 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 present study was designed to investigate a possible GLP-1-renal axis, inducing natriuresis in healthy, volume loaded individuals.

METHODS: Under fixed sodium intake, 8 healthy men were examined twice in random order during a 3-hour infusion of either GLP-1(1.5 pmol kg-1 min-1) 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/release of hormones and ions were measured using Fick's Principle.

RESULTS: During GLP-1 infusion, urinary sodium and osmolar excretions increased significantly compared to 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 subjects, GLP-1 induces significant natriuresis, likely 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.