{"id":"doi:10.1016/j.peptides.2022.170749","kind":"review","title":"GLP-1 and GIP receptor signaling in beta cells – A review of receptor interactions and co-stimulation","authors":["Ashok Mayendraraj","METTE MARIE ROSENKILDE","Lærke S. Gasbjerg"],"author_count":3,"year":2022,"published":"2022-01-19","venue":"Peptides","cited_by":158,"doi":"10.1016/j.peptides.2022.170749","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.peptides.2022.170749","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.peptides.2022.170749","updated":null,"pmid":"35065096","pmcid":null,"openalex_id":"W4206503891","pdf_url":"https://www.sciencedirect.com/science/article/pii/S0196978122000158/pdf","abstract":"Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are two class B1 G protein-coupled receptors, which are stimulated by the gastrointestinal hormones GLP-1 and GIP, respectively. In the pancreatic beta cells, activation of both receptors lead to increased cyclic adenosine monophosphate (cAMP) and glucose-dependent insulin secretion. Marketed GLP-1R agonists such as dulaglutide, liraglutide, exenatide and semaglutide constitute an expanding drug class with beneficial effects for persons suffering from type 2 diabetes and/or obesity. In recent years another drug class, the GLP-1R-GIPR co-agonists, has emerged. Especially the peptide-based, co-agonist tirzepatide is a promising candidate for a better treatment of type 2 diabetes by improving glycemic control and weight reduction. The mechanism of action for tirzepatide include biased signaling of the GLP-1R as well as potent GIPR signaling. Since the implications of co-targeting these closely related receptors concomitantly are challenging to study in vivo, the pharmacodynamic mechanisms and downstream signaling pathways of the GLP-1R-GIPR co-agonists in general, are not fully elucidated. In this review, we present the individual signaling pathways for GLP-1R and GIPR in the pancreatic beta cell with a focus on the shared signaling pathways of the two receptors and interpret the implications of GLP-1R-GIPR co-activation in the light of recent co-activating therapeutic compounds.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Diabetes Treatment and Management"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"GLP-1 and GIP receptor signaling in beta cells – A review of receptor interactions and co-stimulation\" by Ashok Mayendraraj, METTE MARIE ROSENKILDE, Lærke S. Gasbjerg, https://doi.org/10.1016/j.peptides.2022.170749, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"glp1-metabolic","name":"GLP-1 & Incretin Therapies","domain_slug":"medicine"}],"cited_in_dossiers":[]}