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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind106
Udgave nummer1
Sider (fra-til)e11-e19
ISSN0021-972X
DOI
StatusUdgivet - jan. 2021

Bibliografisk note

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

Fingeraftryk

Dyk ned i forskningsemnerne om 'The Renal Extraction and the Natriuretic Action of GLP-1 in Humans Depend on Interaction With the GLP-1 Receptor'. Sammen danner de et unikt fingeraftryk.

Citationsformater