The physiological role of glucagon-like peptide-1 in the regulation of renal function
Open accessAbstract
Glucagon like peptide-1 (GLP-1) is an incretin hormone constantly secreted from the intestine at low basal levels in the fasted state; plasma concentrations rise rapidly after nutrient ingestion. Upon release, GLP-1 exerts insulinotropic effects via a G protein-coupled receptor, stimulation of adenylyl cyclase, and cAMP generation. Although primarily involved in glucose homeostasis, GLP-1 can induce diuresis and natriuresis when administered in pharmacological doses in humans and rodents. However, whether endogenous GLP-1 plays a role in regulating renal function remains an open question. This study aimed to test the hypothesis that blockade of GLP-1 receptor (GLP-1R) signaling at baseline influences renal salt and water handling. To this end, the GLP-1R antagonist exendin-9 (100 μg·kg −1 ·min −1 ) or vehicle was administered intravenously to overnight-fasted male Wistar rats for 30 min. This treatment reduced urinary cAMP excretion and renal cortical PKA activity, demonstrating blockade of renal GLP-1R signaling. Exendin-9-infused-rats exhibited reduced glomerular filtration rate, lithium clearance, urinary volume flow, and sodium excretion compared with vehicle-infused controls. Exendin-9 infusion also reduced renal cortical Na + /H + exchanger isotope 3 (NHE3) phosphorylation at serine 552 (NHE3pS552), a PKA consensus site that correlates with reduced transport activity. Collectively, these results provide novel evidence that GLP-1 is a physiologically relevant natriuretic factor that contributes to sodium balance, in part via tonic modulation of NHE3 activity in the proximal tubule.
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The effects of GLP-1 on urinary volume and sodium excretion could be blocked in mice using a GLP-1 receptor antagonist.
“These effects on urinary volume and sodium excretion could be blocked in mice using a GLP-1 receptor antagonist (31).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [31]
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Rowlands, J., Heng, J., Newsholme, P., & Carlessi, R. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00672 · Cited by 302 · see citing works
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GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity
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“These effects on urinary volume and sodium excretion could be blocked in mice using a GLP-1 receptor antagonist (31).”
GLP-1 mimetics and diabetic ketoacidosis: possible interactions and clinical consequences
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- Authors
- Farah, L. X. S., Valentini, V., Pessoa, T. D., Malnic, G., McDonough, A. A., & Girardi, A. C. C.
- Affiliations
- Heart Institute (InCor), University of São Paulo, São Paulo, Brazil;
- Universidade de São Paulo (BR)
- Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil; and
- University of Southern California (US)
- Corresponding author
- Girardi, Adriana C. C.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2016-01-15
- Volume
- 310
- Issue
- 2
- Pages
- F123-F127
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC5504384
- OpenAlex
- W2340643800
- Cited by
- 111
- References
- 6
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 15 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 13 · 2018: 11 · 2017: 13 · 2016: 5
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk083785-11)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-083785)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- glucagon-like peptide-1, GLP-1 receptor, renal function, sodium excretion, sodium balance, NHE3, Na+/H+ exchanger, cAMP signaling, protein kinase A, glomerular filtration rate, lithium clearance, proximal tubule
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Cyclic AMP, Animals, Glomerular Filtration Rate, Kidney, Male, Natriuresis, Peptide Fragments, Phosphorylation, Signal Transduction, Rats, Wistar, Cyclic AMP-Dependent Protein Kinases, Sodium-Hydrogen Exchangers, Natriuretic Agents, Rats
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