The renal extraction and the natriuretic action of GLP-1 in humans depend on interaction with the GLP-1 receptor

Ali Asmar, Per K Cramon, Meena Asmar, Lene Simonsen, Charlotte M Sorensen, Sten Madsbad, Bolette Hartmann, Jens J Holst, Peter Hovind, Boye L Jensen, Jens Bülow

13 Citations (Scopus)

Abstract

PURPOSE: The natriuretic effect of glucagon-like peptide-1 (GLP-1) in humans is independent of changes in renal plasma flow (RPF) and glomerular filtration rate (GFR) but may involve suppression of angiotensin II (ANG II) and a significant (~45%) renal extraction of GLP-1. The current study was designed to investigate the consequences for the renal extraction and the natriuretic effect of blocking GLP-1 receptors with the specific GLP-1 receptor antagonist, Exendin 9-39 (Ex 9-39).

METHODS: Under fixed sodium intake for 4 days before each study day, 6 healthy male participants were recruited from our recent study where GLP-1 or vehicle was infused (1). In the present new experiments, participants were examined during a 3-hour infusion of GLP-1 (1.5 pmol/kg/min) together with a 3.5-hour infusion of Ex 9-39 (900 pmol/kg/min). Timed urine collections were conducted throughout the experiments. Renal extraction of GLP-1 as well as RPF and GFR were measured via Fick's principle after catheterization of a renal vein. Arterial plasma renin, ANG II, and aldosterone concentrations were measured.

RESULTS: Co-infusion of Ex 9-39 significantly reduced renal extraction of GLP-1 to ~25% compared with GLP-1 infusion alone (~45%). Urinary sodium excretions remained at baseline levels during co-infusion of Ex 9-39 as well as vehicle. By contrast, GLP-1 infusion alone resulted in a 2-fold increase in natriuresis. Ex 9-39 abolished the GLP-1-induced decrease in arterial ANG II concentrations. RPF and GFR remained unchanged during all experiments.

CONCLUSIONS: Renal extraction of GLP-1 and its effect on natriuresis are both dependent on GLP-1 receptor activation in healthy humans.

Original languageEnglish
Article numberdgaa643
JournalThe Journal of clinical endocrinology and metabolism
Volume106
Issue number1
Pages (from-to)e11-e19
Number of pages9
ISSN0021-972X
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • angiotensin II
  • glomerular filtration rate
  • GLP-1
  • kidney
  • natriuresis
  • renal plasma flow

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