ArticlePloS one2012
Allosteric modulation of the activity of the glucagon-like peptide-1 (GLP-1) metabolite GLP-1 9-36 amide at the GLP-1 receptor.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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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
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- The efficacy and safety of liraglutide added to metformin in patients with diabetes: a meta-analysis of randomized controlled trials.Scientific reports · 2016Pooled it
- Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review.Scientific reports · 2016 · on this mapPooled it
- Molecular basis of enhanced GLP-1 signaling mediated by GLP-1(9-36) in conjunction with LSN3318839.Acta pharmaceutica Sinica. B · 2024Article
- Discrepancy between the Actions of Glucagon-like Peptide-1 Receptor Ligands in the Protection of the Heart against Ischemia Reperfusion Injury.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes.British journal of pharmacology · 2022Review
- The metabolite GLP-1 (9-36) is neuroprotective and anti-inflammatory in cellular models of neurodegeneration.Journal of neurochemistry · 2021Article
- Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors.Annual review of pharmacology and toxicology · 2020Review
- Stimulation of GLP-1 Receptor Inhibits Methylglyoxal-Induced Mitochondrial Dysfunctions in H9c2 Cardiomyoblasts: Potential Role of Epac/PI3K/Akt Pathway.Frontiers in pharmacology · 2020Article
- Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes.Pharmacological reviews · 2016Review
- Positive Allosteric Modulation of the Glucagon-like Peptide-1 Receptor by Diverse Electrophiles.The Journal of biological chemistry · 2016Article
- Molecular Characterisation of Small Molecule Agonists Effect on the Human Glucagon Like Peptide-1 Receptor Internalisation.PloS one · 2016Article
- Pancreatic Beta Cell G-Protein Coupled Receptors and Second Messenger Interactions: A Systems Biology Computational Analysis.PloS one · 2016Article
- Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention.Journal of clinical medicine · 2015Review
- A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification.Nature chemical biology · 2014Article
- Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model.Diabetes · 2014Article
- GLP-1(28-36)amide, a Long Ignored Peptide Revisited.The open biochemistry journal · 2014Article
- Regulation of glucose homeostasis by GLP-1.Progress in molecular biology and translational science · 2014Review
- A β-peptide agonist of the GLP-1 receptor, a class B GPCR.Organic letters · 2013Article
- Minireview: Signal bias, allosterism, and polymorphic variation at the GLP-1R: implications for drug discovery.Molecular endocrinology (Baltimore, Md.) · 2013Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucagon-like peptide-1 (GLP-1) released from intestinal L cells in response to nutrients has many physiological effects but particularly enhances glucose-dependent insulin release through the GLP-1 receptor (GLP-1R). GLP-1 7-36 amide, the predominant circulating active form of GLP-1, is rapidly truncated by dipeptidyl peptidase-4 to GLP-1 9-36 amide, which is generally considered inactive. Given its physiological roles, the GLP-1R is targeted for treatment of type 2 diabetes. Recently 'compound 2' has been described as both an agonist and positive allosteric modulator of GLP-1 7-36 amide affinity, but not potency, at the GLP-1R. Importantly, we demonstrated previously that exendin 9-39, generally considered a GLP-1R antagonist, enhances compound 2 efficacy (or vice versa) at the GLP-1R. Given that GLP-1 9-36 amide is the major circulating form of GLP-1 post-prandially and is a low affinity weak partial agonist or antagonist at the GLP-1R, we investigated interaction between this metabolite and compound 2 in a cell line with recombinant expression of the human GLP-1R and the rat insulinoma cell line, INS-1E, with native expression of the GLP-1R. We show compound 2 markedly enhances efficacy and potency of GLP-1 9-36 amide for key cellular responses including AMP generation, Ca(2+) signaling and extracellular signal-regulated kinase. Thus, metabolites of peptide hormones including GLP-1 that are often considered inactive may provide a means of manipulating key aspects of receptor function and a novel therapeutic strategy.
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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.