Cited by 153Receptor Mechanisms and SignalingDiabetes Treatment and ManagementCellular transport and secretion

Real-time trafficking and signaling of the glucagon-like peptide-1 receptor

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Roed, Sarah Noerklit, Wismann, Pernille, Underwood, Christina Rye, Kulahin, Nikolaj, Iversen, Helle, Cappelen, Karen Arevad, Schäffer, Lauge, Lehtonen, Janne +7 more·2014·Molecular and Cellular Endocrinology

Abstract

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.

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Crossref · 10.1016/j.mce.2013.11.010

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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)
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
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

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