ArticleThe Journal of biological chemistry2015
Functional consequences of glucagon-like peptide-1 receptor cross-talk and trafficking.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease-A Systematic Review.International journal of molecular sciences · 2020Pooled it
- Glycemic and bodyweight effects ofScience advances · 2026Article
- Enhancement of a nuclear factor of activated T cells (NFAT) reporter for the study of G protein-coupled receptors.Communications biology · 2026Article
- IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes.Pharmacological research · 2026Review
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- The dual GLP-1 and GIP receptor agonist tirzapetide provides an unintended interaction with the β-adrenoceptors and plays a role in glucose metabolism in hyperglycemic or senescent cardiac cells.Cardiovascular diabetology · 2025Article
- β2-Adrenergic Receptor Utilizes Distinct Interaction Interfaces to Selectively form Heterooligomers with a Subset of Bitter Taste Receptors.Biochemistry · 2025Article
- Glucagon-like Peptide-1 Receptor (GLP-1R) Signaling: Making the Case for a Functionally GInternational journal of molecular sciences · 2025Review
- Endogenous cell membrane interactome mapping for the GLP-1 receptor in different cell types.Nature chemical biology · 2025Article
- Chronic GIPR agonism results in pancreatic islet GIPR functional desensitisation.Molecular metabolism · 2025Article
- Determinants of plasma levels of proglucagon and the metabolic impact of glucagon receptor signalling: a UK Biobank study.Diabetologia · 2024Article
- Revealing the tissue-level complexity of endogenous glucagon-like peptide-1 receptor expression and signaling.Nature communications · 2023Article
- Variation in responses to incretin therapy: Modifiable and non-modifiable factors.Frontiers in molecular biosciences · 2023Review
- Differential effects of glucose-dependent insulinotropic polypeptide receptor/glucagon-like peptide-1 receptor heteromerization on cell signaling when expressed in HEK-293 cells.Pharmacology research & perspectives · 2022Article
- The therapeutic potential of GLP-1 receptor biased agonism.British journal of pharmacology · 2022 · on this mapReview
- GPCR heteromers: An overview of their classification, function and physiological relevance.Frontiers in endocrinology · 2022Review
- Role of a Dual Glucose-Dependent Insulinotropic Peptide (GIP)/Glucagon-like Peptide-1 Receptor Agonist (Twincretin) in Glycemic Control: From Pathophysiology to Treatment.Life (Basel, Switzerland) · 2021Review
- Reagents and models for detecting endogenous GLP1R and GIPR.EBioMedicine · 2021Review
- Acylation of the Incretin Peptide Exendin-4 Directly Impacts Glucagon-Like Peptide-1 Receptor Signaling and Trafficking.Molecular pharmacology · 2021Article
- Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.Molecular metabolism · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signaling capacity of seven-transmembrane/G-protein-coupled receptors (7TM/GPCRs) can be regulated through ligand-mediated receptor trafficking. Classically, the recycling of internalized receptors is associated with resensitization, whereas receptor degradation terminates signaling. We have shown previously that the incretin glucagon-like peptide-1 receptor (GLP-1R) internalizes fast and is primarily resensitized through recycling back to the cell surface. GLP-1R is expressed in pancreatic islets together with the closely related glucose-dependent insulinotropic polypeptide (GIPR) and glucagon (GCGR) receptors. The interaction and cross-talk between coexpressed receptors is a wide phenomenon of the 7TM/GPCR superfamily. Numerous reports show functional consequences for signaling and trafficking of the involved receptors. On the basis of the high structural similarity and tissue coexpression, we here investigated the potential cross-talk between GLP-1R and GIPR or GCGR in both trafficking and signaling pathways. Using a real-time time-resolved FRET-based internalization assay, we show that GLP-1R, GIPR, and GCGR internalize with differential properties. Remarkably, upon coexpression of the internalizing GLP-1R and the non-internalizing GIPR, GLP-1-mediated GLP-1R internalization was impaired in a GIPR concentration-dependent manner. As a functional consequence of such impaired internalization capability, GLP-1-mediated GLP-1R signaling was abrogated. A similar compromised signaling was found when GLP-1R internalization was abrogated by a dominant-negative version of dynamin (dynamin-1 K44E), which provides a mechanistic link between GLP-1R trafficking and signaling. This study highlights the importance of receptor internalization for full functionality of GLP-1R. Moreover, cross-talk between the two incretin receptors GLP-1R and GIPR is shown to alter receptor trafficking with functional consequences for GLP-1R signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.