Fig. 6
From: GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo
Schematic representation of the proposed impact of GRK2 on GLP-1R actions in the β-cell. Upon GLP-1R activation in the β-cell GRK2 is recruited to the activated receptor (1). In a situation of reduced GRK2 dosage or upon stimulation with Gαs-biased agonists (Ex-Phe1), less GRK2 would associate with GLP-1R leading to diminished β-arrestin recruitment (2) and reducing receptor desensitization. Also, these higher levels of free β-arrestin 1 could then activate EPAC2 (3), which would potentiate insulin secretion (4) in a dual manner: contributing to GLP-1R-mediated acute actions on insulin release (Ca2+), as well as increasing the size or efficiency of the RRP. Dotted lines represent indirect mechanisms of action