The Renal Extraction and the Natriuretic Action of GLP-1 in Humans Depend on Interaction With the GLP-1 Receptor

Author:

Asmar Ali12ORCID,Cramon Per K2,Asmar Meena23,Simonsen Lene2,Sorensen Charlotte M4ORCID,Madsbad Sten5,Hartmann Bolette46ORCID,Holst Jens J46ORCID,Hovind Peter12,Jensen Boye L7,Bülow Jens24

Affiliation:

1. Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

2. Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital, University Hospital of Copenhagen, Copenhagen, Denmark

3. Department of Endocrinology, Odense University Hospital, Odense, Denmark

4. Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

5. Department of Endocrinology, Hvidovre Hospital, University Hospital of Copenhagen, Hvidovre, Denmark

6. NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

7. Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark

Abstract

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.

Funder

The Board of Research of Bispebjerg University Hospital

Dagmar Marshalls Foundation

Danish Heart Foundation

Arvid Nilssons Foundation

Novo Nordisk Foundation

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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