G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and are critical regulators of β-cell physiology. Nearly 300 GPCRs are expressed in human islets, where they integrate metabolic, hormonal, neuronal, and inflammatory cues to control insulin secretion, proliferation, and survival. Altered GPCR signaling contributes to β-cell dysfunction and the pathogenesis of both type 1 and type 2 diabetes. This review provides an overview of GPCR functions in β-cell biology, highlighting receptors that stimulate or inhibit glucose-stimulated insulin secretion, as well as those influencing β-cell fate. We also examine GPCR biosynthesis, trafficking, and subcellular localization—processes that shape receptor availability and signaling specificity. Aberrant folding, retention, or misrouting of GPCRs can disrupt β-cell function and contribute to metabolic disease. Thus, beyond receptor pharmacology, understanding the molecular mechanisms governing GPCR biogenesis and spatial distribution is essential for designing targeted strategies to preserve β-cell function and improve glucose homeostasis.
Tecucianu et al. (Thu,) studied this question.