ArticleScience advances2023
Divergent acute versus prolonged pharmacological GLP-1R responses in adult β cell-specific β-arrestin 2 knockout mice.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Evaluating biased agonism of glucagon-like peptide-1 (GLP-1) receptors to improve cellular bioenergetics: A systematic review.Diabetes, obesity & metabolism · 2025Pooled it
- Discovery of Biased Dual-Agonists of Glucagon-Like Peptide 1 and Glucagon Receptors through Mutation of a Conserved Aspartate.ACS medicinal chemistry letters · 2026Article
- Glucagon-like Peptide-1 and Dual GIP/GLP-1 Receptor Agonists in Brain: Exploring the Expanding Role and Safety in Neuropsychiatry.International journal of molecular sciences · 2026Review
- Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations.Molecular metabolism · 2026Article
- In vivo functional profiling and structural characterization of the humanScience advances · 2026Article
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Multi-faceted roles of β-arrestins in G protein-coupled receptor endocytosis.Nature communications · 2025Article
- Hypoglycemic effect ofGut microbes · 2025Article
- Review
- Binding kinetics, bias, receptor internalization and effects on insulin secretion in vitro and in vivo of a novel GLP-1R/GIPR dual agonist, HISHS-2001.Diabetes, obesity & metabolism · 2025Article
- Glucagon-like Peptide-1 Receptor (GLP-1R) Signaling: Making the Case for a Functionally GInternational journal of molecular sciences · 2025Review
- Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy.Cell reports. Medicine · 2025Article
- Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells.eLife · 2025Article
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- Does Incretin Agonism Have Sustainable Efficacy?Cells · 2024Review
- New insights into the regulation of GIPR signalling.Nature reviews. Endocrinology · 2024Article
- Characterization of genetic variants of GIPR reveals a contribution of β-arrestin to metabolic phenotypes.Nature metabolism · 2024Article
- Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don't.Physiology (Bethesda, Md.) · 2024Review
- GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells.Peptides · 2024Article
- An imbalanced GLP-1R/GIPR co-agonist peptide with a site-specific N-terminal PEGylation to maximize metabolic benefits.iScience · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
The glucagon-like peptide-1 receptor (GLP-1R) is a major type 2 diabetes therapeutic target. Stimulated GLP-1Rs are rapidly desensitized by β-arrestins, scaffolding proteins that not only terminate G protein interactions but also act as independent signaling mediators. Here, we have assessed in vivo glycemic responses to the pharmacological GLP-1R agonist exendin-4 in adult β cell-specific β-arrestin 2 knockout (KO) mice. KOs displayed a sex-dimorphic phenotype consisting of weaker acute responses that improved 6 hours after agonist injection. Similar effects were observed for semaglutide and tirzepatide but not with biased agonist exendin-phe1. Acute cyclic adenosine 5'-monophosphate increases were impaired, but desensitization reduced in KO islets. The former defect was attributed to enhanced β-arrestin 1 and phosphodiesterase 4 activities, while reduced desensitization co-occurred with impaired GLP-1R recycling and lysosomal targeting, increased trans-Golgi network signaling, and reduced GLP-1R ubiquitination. This study has unveiled fundamental aspects of GLP-1R response regulation with direct application to the rational design of GLP-1R-targeting therapeutics.
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Registered trials
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 Socratic graph.