Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells
Abstract
Background GLP-1 is secreted into the circulation after food intake. The main biological effects of GLP-1 include stimulation of glucose dependent insulin secretion and induction of satiety feelings. Recently, it was demonstrated in rats and humans that GLP-1 can stimulate renal excretion of sodium. Based on these data, the existence of a renal GLP-1 receptor (GLP-1R) was postulated. However, the exact localization of the GLP-1R and the mechanism of this GLP-1 action have not yet been investigated. Methods Primary porcine proximal tubular cells were isolated from porcine kidneys. Expression of GLP-1R was measured at the mRNA level by quantitative RT-PCR. Protein expression of GLP-1R was verified with immunocytochemistry, immunohistochemistry and Western blot analysis. Functional studies included transport assessments of sodium and glucose using three different GLP-1 concentrations (200 pM, 2 nM and 20 nM), 200 pM exendin-4 (GLP-1 analogue) and an inhibitor of the dipeptidylpeptidase IV (DPPIV) enzyme (P32/98 at 10 microM). Finally, the expression of NHE3, the predominant Na(+)/H(+) exchanger in proximal tubular cells, was also investigated. Results GLP-1R, NHE3 and DPPIV were expressed at the mRNA level in porcine proximal tubular kidney cells. GLP-1R expression was confirmed at the protein level. Staining of human and pig kidney cortex revealed that GLP-1R was predominantly expressed in proximal tubular cells. Functional assays demonstrated an inhibition of sodium re-absorption with GLP-1 after 3 h of incubation. Exendin-4 and GLP-1 in combination with P32/98 co-administration had no clear influence on glucose and sodium uptake and transport. Conclusion GLP-1R is functionally expressed in porcine proximal tubular kidney cells. Addition of GLP-1 to these cells resulted in a reduced sodium re-absorption. GLP-1 had no effect on glucose re-absorption. We conclude that GLP-1 modulates sodium homeostasis in the kidney most likely through a direct action via its GLP-1R in proximal tubular cells.
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The GLP-1 receptor is expressed in glomerular capillaries and vascular walls of the mouse kidney and in the glomerulus and proximal convoluted tubules of the rat and pig.
“The GLP-1 receptor is expressed in glomerular capillaries and vascular walls of the mouse kidney [14, 101] and in the glomerulus and proximal convoluted tubules of the rat and pig [29, 102].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [102]
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References 41 · Cited by 149
- Authors
- Schlatter, P., Beglinger, C., Drewe, J., & Gutmann, H.
- Affiliations
- University Hospital of Basel (CH)
- Corresponding author
- Drewe, J.
- Venue
- Regulatory Peptides
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 141
- Issue
- 1-3
- Pages
- 120-128
- ISSN
- 0167-0115 (ISSN-L)
- OpenAlex
- W2052301782
- Cited by
- 149
- References
- 41
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 13 · 2019: 11 · 2018: 5 · 2017: 12 · 2016: 9 · 2015: 14 · 2014: 11 · 2013: 14 · 2012: 6
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Peptides (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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 › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- GLP-1 receptor, glucagon-like peptide-1, proximal tubular epithelial cells, sodium reabsorption, sodium homeostasis, NHE3, dipeptidyl peptidase IV, exendin-4, glucose reabsorption, renal sodium transport, porcine kidney
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Sodium-Hydrogen Exchanger 3, Exenatide, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Inhibitors, Glucose, Immunohistochemistry, Kidney Tubules, Proximal, Kinetics, Pentanoic Acids, Peptides, RNA, Messenger, Sodium, Swine, Venoms, Blotting, Western, Sodium-Hydrogen Exchangers, Receptors, Glucagon, Cell Culture Techniques, Reverse Transcriptase Polymerase Chain Reaction, Glucagon-Like Peptide 1, Thiazolidines, Dipeptidyl-Peptidase IV Inhibitors
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