Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

Background And Purpose: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic β cells activates the CRF receptor (CRFR) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis.

Experimental Approach: Here, we used Arrb1, Arrb2, Gs and Gq knockout mice, the G-shRNA-GFP lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of G, G and β-arrestin1 to CRFR contributed to UCN3-induced SST secretion in pancreatic δ cells.

Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.

The ankle-link complex (ALC) consists of USH2A, WHRN, PDZD7, and ADGRV1 and plays an important role in hair cell development. At present, its architectural organization and signaling role remain unclear. By establishing Adgrv1 Y6236fsX1 mutant mice as a model of the deafness-associated human Y6244fsX1 mutation, the authors show here that the Y6236fsX1 mutation disrupts the interaction between adhesion G protein-coupled receptor V subfamily member 1 (ADGRV1) and other ALC components, resulting in stereocilia disorganization and mechanoelectrical transduction (MET) deficits.

Endogenous Lipid-GPR120 Signaling Modulates Pancreatic Islet Homeostasis to Different Extents.

Long-chain fatty acids (LCFAs) are not only energy sources but also serve as signaling molecules. GPR120, an LCFA receptor, plays key roles in maintaining metabolic homeostasis. However, whether endogenous ligand-GPR120 circuits exist and how such circuits function in pancreatic islets are unclear.

Structures of the glucocorticoid-bound adhesion receptor GPR97-G complex.

Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97), a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-G complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain.

In vitro expansion of pancreatic islet clusters facilitated by hormones and chemicals.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalised drug testing. However, such a strategy has not been realised yet. Propagation could be divided into two steps, in vitro expansion and repeated passaging.