New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling.

Harnessing the translational potential of the GLP-1/GLP-1R system in pancreatic beta cells has led to the development of established GLP-1R-based therapies for the long-term preservation of beta cell function. In this review, we discuss recent advances in the current research on the GLP-1/GLP-1R system in beta cells, including the regulation of signaling by endocytic trafficking as well as the application of concepts such as signal bias, allosteric modulation, dual agonism, polymorphic receptor variants, spatial compartmentalization of cAMP signaling and new downstream signaling targets involved in the control of beta cell function. Unlabelled Image • GLP-1R signaling can be regulated by a number of biological processes. • These include modulation of receptor trafficking and conformational dynamics. • Dual/triple GLP-1RAs activating additional GPCRs have recently been developed. • GLP-1R cAMP signaling is compartmentalized by ACs, PDEs and AKAPs. • GLP-1R-induced cAMP activates multiple pathways to regulate beta cell function. [ABSTRACT FROM AUTHOR]