GPR162 is a beta cell CART receptor

Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knock-down (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We there-fore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was es-tablished using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding. Gpr162 KD cells had blunted CARTp-induced exocytosis, and reduced CARTp-induced insulin secretion. Furthermore, we identified a hitherto undescribed GPR162-dependent role of CART as a regulator of cytoskeletal arrangement. Thus, our findings provide mech-anistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.

Automated summary

CART is expressed in pancreatic islet cells and neuronal elements, and has insulinotropic effects. We identified GPR162 as the receptor that mediates the effects of CART in pancreatic beta cells. Silencing GPR162 reduced the binding of CART to the receptor and attenuated CART-induced exocytosis and insulin secretion. Furthermore, CART was found to regulate cytoskeletal arrangement through GPR162.