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GPR162 is a beta cell CART receptor.

Andreas Lindqvist1, Mia Abels1, Liliya Shcherbina1

  • 1Neuroendocrine Cell Biology, Lund University Diabetes Centre, Department for Experimental Medical Science, Lund University, CRC, Malmö, Sweden.

Iscience
|December 11, 2023
PubMed
Summary

Cocaine and amphetamine-regulated transcript (CART) signaling in pancreatic beta cells is mediated by G protein-coupled receptor 162 (GPR162). This study identifies GPR162 as the CART receptor, crucial for insulin secretion and cytoskeletal regulation.

Keywords:
Biological sciencesEndocrinologyNatural sciencesPhysiology

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Cocaine and amphetamine-regulated transcript (CART) is known to influence insulin secretion in pancreatic islets.
  • The specific receptor for CART in pancreatic beta cells has remained unidentified.
  • Previous work established insulinotropic actions of CART in human and rodent islets.

Purpose of the Study:

  • To identify the receptor mediating CART's effects in pancreatic beta cells.
  • To investigate the role of G protein-coupled receptor 162 (GPR162) in CART signaling.
  • To elucidate the mechanisms by which CART influences insulin secretion and cellular function.

Main Methods:

  • RNA sequencing of Cartpt knockdown INS-1 832/13 cells to identify potential receptors.
  • Binding assays including proximity ligation assay, radioactive binding, and co-immunoprecipitation to confirm CART-GPR162 interaction.
  • Gpr162 knockdown experiments to assess the functional impact on CART-mediated effects.
  • Analysis of insulin secretion and cytoskeletal arrangement in response to CART stimulation.

Main Results:

  • GPR162 was identified as the most Cartpt-regulated receptor via RNA sequencing.
  • CART binding to GPR162 was confirmed using multiple biochemical and proximity assays.
  • Gpr162 knockdown resulted in reduced CART binding, blunted CART-induced exocytosis, and decreased insulin secretion.
  • A novel GPR162-dependent role for CART in regulating cytoskeletal arrangement was discovered.

Conclusions:

  • G protein-coupled receptor 162 (GPR162) is identified as the functional receptor for Cocaine and amphetamine-regulated transcript (CART) in pancreatic beta cells.
  • GPR162 mediates CART's effects on insulin secretion, exocytosis, and cytoskeletal organization.
  • These findings provide crucial mechanistic insights into CART-regulated beta cell function.