Oxyntomodulin differentially affects glucagon-like peptide-1 receptor beta-arrestin recruitment and signaling through Galpha(s)

Research output: Contribution to journalJournal articleResearchpeer-review

Rasmus Jorgensen, Valentina Kubale, Milka Vrecl, Thue W Schwartz, Christian E Elling

The glucagon-like peptide (GLP)-1 receptor is a promising target for the treatment of type 2 diabetes and obesity, and there is great interest in characterizing the pharmacology of the GLP-1 receptor and its ligands. In the present report, we have applied bioluminescence resonance energy transfer assays to measure agonist-induced recruitment of betaarrestins and G-protein-coupled receptor kinase (GRK) 2 to the GLP-1 receptor in addition to traditional measurements of second messenger generation. The peptide hormone oxyntomodulin is described in the literature as a full agonist on the glucagon and GLP-1 receptors. Surprisingly, despite being full agonists in GLP-1 receptor-mediated cAMP accumulation, oxyntomodulin and glucagon were observed to be partial agonists in recruiting betaarrestins and GRK2 to the GLP-1 receptor. We suggest that oxyntomodulin and glucagon are biased ligands on the GLP-1 receptor.
Original languageEnglish
JournalJournal of Pharmacology and Experimental Therapeutics
Volume322
Issue number1
Pages (from-to)148-54
Number of pages6
ISSN0022-3565
DOIs
Publication statusPublished - 2007

Bibliographical note

Keywords: Animals; Arrestins; COS Cells; Cercopithecus aethiops; Cyclic AMP; G-Protein-Coupled Receptor Kinase 2; G-Protein-Coupled Receptor Kinase 5; GTP-Binding Protein alpha Subunits, Gs; Glucagon; Glucagon-Like Peptide 1; Humans; Luminescent Measurements; Oxyntomodulin; Protein-Serine-Threonine Kinases; Receptors, Glucagon; Signal Transduction; beta-Adrenergic Receptor Kinases

ID: 21666285