TY - JOUR

T1 - The Renal Extraction and the Natriuretic Action of GLP-1 in Humans Depend on Interaction With the GLP-1 Receptor

AU - Asmar, Ali

AU - Cramon, Per K

AU - Asmar, Meena

AU - Simonsen, Lene

AU - Sørensen, Charlotte M

AU - Madsbad, Sten

AU - Hartmann, Bolette

AU - Holst, Jens J

AU - Hovind, Peter

AU - Jensen, Boye L

AU - Bülow, Jens

N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2021

Y1 - 2021

N2 - PURPOSE: The natriuretic effect of 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.

AB - PURPOSE: The natriuretic effect of 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.

U2 - 10.1210/clinem/dgaa643

DO - 10.1210/clinem/dgaa643

M3 - Journal article

C2 - 32927478

VL - 106

SP - e11-e19

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -