Rewiring β2-adrenergic receptor signaling: harnessing non-canonical GRK functions to treat metabolic diseases

Abstract

In a study published recently in Cell, Motso et al.¹ developed a series of G protein-coupled receptor kinase 2 (GRK2)-biased agonists for the β₂-adrenergic receptor (β₂AR) which showed efficacy in stimulating muscular glucose uptake without eliciting cardiac side effects typically associated with systemically applied β-agonists.² The candidate drug, compound 15, was well-tolerated in a phase 1 clinical trial and could provide a promising alternative treatment option for type 2 diabetes and obesity.¹