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

J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Drinking / physiology
  • Glomerular Filtration Rate / physiology
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / metabolism*
  • Healthy Volunteers
  • Humans
  • Infusions, Intravenous
  • Kidney Tubules / physiology*
  • Male
  • Natriuresis / physiology*
  • Renal Plasma Flow / physiology
  • Young Adult

Substances

  • Glucagon-Like Peptide 1