PMID- 38077141
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231211
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 26
IP  - 12
DP  - 2023 Dec 15
TI  - GPR162 is a beta cell CART receptor.
PG  - 108416
LID - 10.1016/j.isci.2023.108416 [doi]
LID - 108416
AB  - 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.
CI  - (c) 2023 The Author(s).
FAU - Lindqvist, Andreas
AU  - Lindqvist A
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Abels, Mia
AU  - Abels M
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Shcherbina, Liliya
AU  - Shcherbina L
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Ngara, Mtakai
AU  - Ngara M
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Kryvokhyzha, Dmytro
AU  - Kryvokhyzha D
AD  - Diabetic Complications, Lund University Diabetes Centre, Department of Clinical 
      Sciences Malmo, Lund University, CRC, Malmo, Sweden.
FAU - Chriett, Sabrina
AU  - Chriett S
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Riva, Matteo
AU  - Riva M
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Fajul, Abul
AU  - Fajul A
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
FAU - Barghouth, Mohammad
AU  - Barghouth M
AD  - Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical 
      Sciences Malmo, Lund University, CRC, Malmo, Sweden.
FAU - Luan, Cheng
AU  - Luan C
AD  - Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical 
      Sciences Malmo, Lund University, CRC, Malmo, Sweden.
FAU - Eliasson, Lena
AU  - Eliasson L
AD  - Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical 
      Sciences Malmo, Lund University, CRC, Malmo, Sweden.
FAU - Larsen, Olav
AU  - Larsen O
AD  - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Rosenkilde, Mette M
AU  - Rosenkilde MM
AD  - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Zhang, Enming
AU  - Zhang E
AD  - Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical 
      Sciences Malmo, Lund University, CRC, Malmo, Sweden.
FAU - Renstrom, Erik
AU  - Renstrom E
AD  - Islet Pathophysiology, Lund University Diabetes Centre, Department of Clinical 
      Sciences Malmo, Lund University, CRC, Malmo, Sweden.
FAU - Wierup, Nils
AU  - Wierup N
AD  - Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for 
      Experimental Medical Science, Lund University, CRC, Malmo, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20231110
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC10709007
OTO - NOTNLM
OT  - Biological sciences
OT  - Endocrinology
OT  - Natural sciences
OT  - Physiology
COIS- The authors declare no competing interests.
EDAT- 2023/12/11 12:43
MHDA- 2023/12/11 12:44
PMCR- 2023/11/10
CRDT- 2023/12/11 06:25
PHST- 2023/07/13 00:00 [received]
PHST- 2023/09/29 00:00 [revised]
PHST- 2023/11/06 00:00 [accepted]
PHST- 2023/12/11 12:44 [medline]
PHST- 2023/12/11 12:43 [pubmed]
PHST- 2023/12/11 06:25 [entrez]
PHST- 2023/11/10 00:00 [pmc-release]
AID - S2589-0042(23)02493-8 [pii]
AID - 108416 [pii]
AID - 10.1016/j.isci.2023.108416 [doi]
PST - epublish
SO  - iScience. 2023 Nov 10;26(12):108416. doi: 10.1016/j.isci.2023.108416. eCollection 
      2023 Dec 15.