title: The complexity of signalling mediated by the glucagon-like peptide-1 receptor.
abstract: The glucagon-like peptide-1 receptor (GLP-1R) is a class B GPCR that is a major therapeutic target for the treatment of type 2 diabetes. The receptor is activated by the incretin peptide GLP-1 promoting a broad range of physiological effects including glucose-dependent insulin secretion and biosynthesis, improved insulin sensitivity of peripheral tissues, preservation of β-cell mass and weight loss, all of which are beneficial in the treatment of type 2 diabetes. Despite this, existing knowledge surrounding the underlying signalling mechanisms responsible for the physiological actions downstream of GLP-1R activation is limited. Here, we review the current understanding around GLP-1R-mediated signalling, in particular highlighting recent contributions to the field on biased agonism, the spatial and temporal aspects for the control of signalling and how these concepts may influence future drug development.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, Melbourne, 3052, Australia.
authors.forename: Madeleine M
authors.initials: MM
authors.lastname: Fletcher
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, Melbourne, 3052, Australia.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Halls
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, Melbourne, 3052, Australia.
authors.forename: Arthur
authors.initials: A
authors.lastname: Christopoulos
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, Melbourne, 3052, Australia.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sexton
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, Melbourne, 3052, Australia denise.wootten@monash.edu.
authors.forename: Denise
authors.initials: D
authors.lastname: Wootten
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004705:Endocytosis; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D015398:Signal Transduction
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D008024:Ligands
keywords: G protein-coupled receptor; biased signalling; glucagon-like peptide-1 receptor; ligand-directed signalling bias