M3-muscarinic receptor promotes insulin release via receptor phosphorylation/arrestin-dependent activation of protein kinase D1

摘要: The activity of G protein-coupled receptors is regulated via hyper-phosphorylation following agonist stimulation. Despite the universal nature this regulatory process, physiological impact receptor phosphorylation remains poorly studied. To address question, we have generated a knock-in mouse strain that expresses phosphorylation-deficient mutant M(3)-muscarinic receptor, prototypical G(q/11)-coupled receptor. This was used here to investigate role in regulation insulin secretion from pancreatic islets. Importantly, deficient coupled G(q/11)-signaling pathways but uncoupled phosphorylation-dependent processes, such as internalization and β-arrestin recruitment. mice showed impaired glucose tolerance secretion, indicating expressed on islets regulate homeostasis phosphorylation-/arrestin-dependent signaling. mechanism centers activation protein kinase D1, which operates downstream recruitment phosphorylated In conclusion, our findings support unique concept receptor-mediated augmentation sustained release largely independent protein-coupling involves coupling D1.