The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index.
Real-time trafficking and signaling of the glucagon-like peptide-1 receptor
Open accessAbstract
The glucagon-like peptide-1 incretin receptor (GLP-1R) of family B G protein-coupled receptors (GPCRs) is a major drug target in type-2-diabetes due to its regulatory effect on post-prandial blood-glucose levels. The mechanism(s) controlling GLP-1R mediated signaling are far from fully understood. A fundamental mechanism controlling the signaling capacity of GPCRs is the post-endocytic trafficking of receptors between recycling and degradative fates. Here, we combined microscopy with novel real-time assays to monitor both receptor trafficking and signaling in living cells. We find that the human GLP-1R internalizes rapidly and with similar kinetics in response to equipotent concentrations of GLP-1 and the stable GLP-1 analogues exendin-4 and liraglutide. Receptor internalization was confirmed in mouse pancreatic islets. GLP-1R is shown to be a recycling receptor with faster recycling rates mediated by GLP-1 as compared to exendin-4 and liraglutide. Furthermore, a prolonged cycling of ligand-activated GLP-1Rs was observed and is suggested to be correlated with a prolonged cAMP signal.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Each receptor undergoes agonist-induced endocytosis to varying degrees, thus fine-tuning spatial and temporal modulation of intracellular signaling and hormonal response [28].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [28]
Citations
Cites
The Physiology of Glucagon-like Peptide 1
Holst, J. J. (2007) · Physiological Reviews · doi:10.1152/physrev.00034.2006 · Cited by 3,371
Pathways and mechanisms of endocytic recycling
Grant, B. D., & Donaldson, J. G. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2755 · Cited by 1,424
Molecular and Cellular Endocrinology
Rainey, W. E., & Rodgers, R. J. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2004.10.007 · Cited by 1,340
GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus
Meier, J. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.140 · Cited by 1,311
Kieffer, T. J., McIntosh, C. H., & Pederson, R. A. (1995) · Endocrinology · doi:10.1210/endo.136.8.7628397 · Cited by 1,124
Göke, R., Fehmann, H. C., Linn, T., Schmidt, H., Krause, M., Eng, J., & Göke, B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36565-2 · Cited by 837
Conformational biosensors reveal GPCR signalling from endosomes
Irannejad, R., Tomshine, J. C., Tomshine, J. R., Chevalier, M., Mahoney, J. P., Steyaert, J., Rasmussen, S. G. F., Sunahara, R. K., El-Samad, H., Huang, B., et al. (2013) · Nature · doi:10.1038/nature12000 · Cited by 819
Regulation of GPCRs by Endocytic Membrane Trafficking and Its Potential Implications
Hanyaloglu, A. C., & von Zastrow, M. (2007) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094830 · Cited by 610
International Union of Pharmacology. XXXV. The Glucagon Receptor Family
Mayo, K. E., Miller, L. J., BATAILLE, D., Dalle, S., Göke, B., Thorens, B., & Drucker, D. J. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.1.6 · Cited by 514
Maurel, D., Comps‐Agrar, L., Brock, C., Rives, M., Bourrier, E., Ayoub, M. A., Bazin, H., Tinel, N., Durroux, T., Prézeau, L., et al. (2008) · Nature Methods · doi:10.1038/nmeth.1213 · Cited by 500
Cited by
Sorted by citations
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Secher, A., Jelsing, J., Baquero, A. F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L. S., Hansen, G., Grove, K. L., Pyke, C., Raun, K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75276 · Cited by 961
Self-citationGraaf, C. D., Donnelly, D., Wootten, D., Lau, J., Sexton, P. M., Miller, L. J., Ahn, J.-M., Liao, J., Fletcher, M. M., Yang, D., et al. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011395 · Cited by 403
Biased Receptor Signaling in Drug Discovery
Kenakin, T. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.016790 · Cited by 321
Targeting GLP-1 receptor trafficking to improve agonist efficacy
Jones, B. J., Buenaventura, T., Kanda, N., CHABOSSEAU, P. L., Owen, B. M., Scott, R., Goldin, R. D., Angkathunyakul, N., Junior, I. R. C., Bosco, D., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03941-2 · Cited by 274
The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders
Klausen, M. K., Thomsen, M., Wortwein, G., & Fink‐Jensen, A. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15677 · Cited by 259
Metadata
- Authors
- Roed, S. N., Wismann, P., Underwood, C. R., Kulahin, N., Iversen, H., Cappelen, K. A., Schäffer, L., Lehtonen, J., Hecksher-Soerensen, J., Secher, A., Mathiesen, J. M., Bräuner-Osborne, H., Whistler, J. L., Knudsen, S. M., & Waldhoer, M.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- University of Copenhagen (DK)
- University of California, San Francisco (US)
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 382
- Issue
- 2
- Pages
- 938-949
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W1987856394
- Cited by
- 153
- References
- 25
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 7 · 2023: 8 · 2022: 14 · 2021: 16 · 2020: 17 · 2019: 15 · 2018: 11 · 2017: 9 · 2016: 13 · 2015: 13 · 2014: 9
- FWCI
- 5.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular and Cellular Endocrinology (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Lundbeckfonden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- GLP-1 receptor, G protein-coupled receptors, receptor internalization, receptor recycling, receptor trafficking, exendin-4, liraglutide, GLP-1 analogues, cAMP signaling, pancreatic islets, type 2 diabetes
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Liraglutide, Exenatide, Cyclic AMP, Animals, Humans, Islets of Langerhans, Mice, Inbred C57BL, Peptides, Venoms, Signal Transduction, Receptors, Glucagon, Protein Transport, Mice, Glucagon-Like Peptide 1, Incretins, Protein Stability, HEK293 Cells, Time-Lapse Imaging, Proteolysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
