ArticleDiabetologia2018
Development and characterisation of a novel glucagon like peptide-1 receptor antibody.
Article in Diabetologia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.Cell reports · 2019Trial
- Incretin-Based Therapies, Obesity-Associated Inflammation, and Atherosclerotic Cardiovascular Risk.Cells · 2026Review
- scFv-based biologics in diabetes: from therapeutic potential to clinical prospects.Frontiers in immunology · 2026Review
- Glucagon-Like Peptide 1 Receptor Agonist Stimulation Inhibits Laser-Induced Choroidal Neovascularization by Suppressing Intraocular Inflammation.Investigative ophthalmology & visual science · 2025Article
- The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.Nature communications · 2024Article
- Comparative Analysis of Orthosteric and Allosteric GLP-1R Agonists' Effects on Insulin Secretion from Healthy, Diabetic, and Recovered INS-1E Pancreatic Beta Cells.International journal of molecular sciences · 2024Article
- GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells.Peptides · 2024Article
- Dorothy Hodgkin lecture 2023: The enteroendocrine system-Sensors in your guts.Diabetic medicine : a journal of the British Diabetic Association · 2023Review
- Article
- Revealing the tissue-level complexity of endogenous glucagon-like peptide-1 receptor expression and signaling.Nature communications · 2023Article
- Ginsenoside Rb1 Promotes Hepatic Glycogen Synthesis to Ameliorate T2DM Through 15-PGDH/PGEDiabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- Metabolic responses and benefits of glucagon-like peptide-1 (GLP-1) receptor ligands.British journal of pharmacology · 2022Review
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- Reagents and models for detecting endogenous GLP1R and GIPR.EBioMedicine · 2021Review
- The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1.Journal of proteome research · 2021Article
- Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms.Molecular metabolism · 2021Review
- Detection of genome-edited and endogenously expressed G protein-coupled receptors.The FEBS journal · 2021Review
- Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation.Endocrine reviews · 2021Review
- Discordance between GLP-1R gene and protein expression in mouse pancreatic islet cells.The Journal of biological chemistry · 2020Article
- Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisGlucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo.
methodsA naive phage display selection strategy was used to isolate single-chain variable fragments (ScFvs) that bound to GLP1R. The ScFv with the highest affinity, Glp1R0017, was converted into a human IgG1 and characterised further. In vitro antagonistic activity was assessed in a number of assays: a cAMP-based homogenous time-resolved fluorescence assay in GLP1R-overexpressing cell lines, a live cell cAMP imaging assay and an insulin secretion assay in INS-1 832/3 cells. Glp1R0017 was further tested in immunostaining of mouse pancreas, and the ability of Glp1R0017 to block GLP1R in vivo was assessed by both IPGTT and OGTT in C57/Bl6 mice.
resultsAntibodies to GLP1R were selected from naive antibody phage display libraries. The monoclonal antibody Glp1R0017 antagonised mouse, human, rat, cynomolgus monkey and dog GLP1R. This antagonistic activity was specific to GLP1R; no antagonistic activity was found in cells overexpressing the glucose-dependent insulinotropic peptide receptor (GIPR), glucagon like peptide-2 receptor or glucagon receptor. GLP-1-stimulated cAMP and insulin secretion was attenuated in INS-1 832/3 cells by Glp1R0017 incubation. Immunostaining of mouse pancreas tissue with Glp1R0017 showed specific staining in the islets of Langerhans, which was absent in Glp1r knockout tissue. In vivo, Glp1R0017 reversed the glucose-lowering effect of liraglutide during IPGTTs, and reduced glucose tolerance by blocking endogenous GLP-1 action in OGTTs. CONCLUSIONS/
interpretationGlp1R0017 is a monoclonal antagonistic antibody to the GLP1R that binds to GLP1R on pancreatic beta cells and blocks the actions of GLP-1 in vivo. This antibody holds the potential to be used in investigating the physiological importance of GLP1R signalling in extrapancreatic tissues where cellular targets and signalling pathways activated by GLP-1 are poorly understood.
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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 OpenQuestion graph.