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The Renal Extraction and the Natriuretic Action of GLP-1 in Humans Depend on Interaction With the GLP-1 Receptor
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.
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Glucagon-like peptide-1 receptor agonism produces a direct effect to promote urinary sodium excretion, independent of changes in adipose tissue volume.
“However, in the case of tirzepatide, it is noteworthy that glucagon-like peptide-1 receptor agonism produces a direct effect itself to promote urinary sodium excretion, independent of changes in adipose tissue volume38,39.”
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Borlaug, B. A., Zile, M. R., Kramer, C. M., Baum, S. J., Hurt, K., Litwin, S. E., Murakami, M., Ou, Y., Upadhyay, N., & Packer, M. (2025) · Nature Medicine · doi:10.1038/s41591-024-03374-z · Cited by 166
Effects of SGLT2 inhibitors and GLP-1 receptor agonists on renin-angiotensin-aldosterone system
Puglisi, S., Rossini, A., Poli, R., Dughera, F., Pia, A., Terzolo, M., & Reimondo, G. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.738848 · Cited by 143
Metadata
- Authors
- Asmar, A., Cramon, P. K., Asmar, M., Simonsen, L., Sorensen, C. M., Madsbad, S., Hartmann, B., Holst, J. J., Hovind, P., Jensen, B. L., & Bülow, J.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2020-09-14
- Volume
- 106
- Issue
- 1
- Pages
- e11-e19
- ISSN
- 0021-972X
- 1945-7197
- Cited by
- 27
- References
- 5
- Language
- en
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Funders
- The Board of Research of Bispebjerg University Hospital
- Dagmar Marshalls Foundation
- Danish Heart Foundation
- Arvid Nilssons Foundation
- Novo Nordisk Foundation
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