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Pontus Dunér

Assistant researcher

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Adhesion G protein-coupled receptor G1 (ADGRG1/GPR56) and pancreatic β-cell function

Author

  • Pontus Dunér
  • Israa Mohammed
  • Arvind Soni
  • Olof Asplund
  • Fatemeh Safi
  • Petter Storm
  • Leif Groop
  • Stefan Amisten
  • S Albert Salehi

Summary, in English

Context: Adhesion G protein-coupled receptor (GPCR)-G1 (ADGRG1) is the most abundant GPCR in human pancreatic islets, but its role in islet function is unclear. Objective: Investigate how ADGRG1 expression and activation by its ligand, collagen III, impacts β-cell function in normal and type 2 diabetic (T2D) islets. Design: Genes associated with the ADGRG1 in human islets was probed by RNA-sequencing of human pancreatic islet isolated from cadaveric donors, followed by functional studies on β-cell proliferation, apoptosis, and insulin secretion in human and mouse islets and in INS-1 cells. Main Outcome Measures: Changes in β-cell gene expression, proliferation, apoptosis, and insulin secretion were quantified by RNA-sequencing, qPCR, Thymidine incorporation, Western blotting, and RIA, respectively. Results: ADGRG1 is the most abundant GPCR mRNA in both human and mouse islets, and its expression inhumanislets strongly correlates with genes important for β-cell function and T2 Drisk. Theexpression ofADGRG1wasreduced in islets ofT2Ddonors, in db/dbmouseislets,andin isolated human islets exposed to chronic hyperglycemia. Beneficial effects of collagen type III on β-cell function via activation of the cAMP/protein kinase A pathway, suppression of RhoA and caspase-3 activity, increased β-cell viability, and proliferation were abolished when ADGRG1 was downregulated in β-cells. Conclusions:Wedemonstrate a mechanistic link between ADGRG1 expression andβ-cell function. Pharmacological agents that promote expression or activation of the ADGRG1 receptor may represent a novel approach for the treatment of T2D.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis
  • Islet cell physiology
  • Genomics, Diabetes and Endocrinology
  • Division of Molecular Hematology (DMH)
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2016-12-01

Language

English

Pages

4637-4645

Publication/Series

Journal of Clinical Endocrinology and Metabolism

Volume

101

Issue

12

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Pharmacology and Toxicology
  • Endocrinology and Diabetes

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis
  • Islet cell physiology
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 0021-972X