Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Mia Abels
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Liliya Shcherbina
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Mtakai Ngara
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Dmytro Kryvokhyzha
Diabetic Complications, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, CRC, Malmö, Sweden
Sabrina Chriett
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Matteo Riva
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Abul Fajul
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden
Mohammad Barghouth
Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, CRC, Malmö, Sweden
Cheng Luan
Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, CRC, Malmö, Sweden
Lena Eliasson
Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, CRC, Malmö, Sweden
Olav Larsen
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Mette M. Rosenkilde
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Enming Zhang
Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, CRC, Malmö, Sweden
Erik Renström
Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, CRC, Malmö, Sweden
Nils Wierup
Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden; Corresponding author
Summary: 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 knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established 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 mechanistic insight into the effect of CART on insulin secretion and show that GPR162 is the CART receptor in beta cells.
