title: Adhesion G Protein-Coupled Receptor G1 (ADGRG1/GPR56) and Pancreatic β-Cell Function.
abstract: 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.
  
  
  
  Investigate how ADGRG1 expression and activation by its ligand, collagen III, impacts β-cell function in normal and type 2 diabetic (T2D) islets.
  
  
  
  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.
  
  
  
  Changes in β-cell gene expression, proliferation, apoptosis, and insulin secretion were quantified by RNA-sequencing, qPCR, Thymidine incorporation, Western blotting, and RIA, respectively.
  
  
  
  ADGRG1 is the most abundant GPCR mRNA in both human and mouse islets, and its expression in human islets strongly correlates with genes important for β-cell function and T2D risk. The expression of ADGRG1 was reduced in islets of T2D donors, in db/db mouse islets, and in 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 down-regulated in β-cells.
  
  
  
  We demonstrate a mechanistic link between ADGRG1 expression and β-cell function. Pharmacological agents that promote expression or activation of the ADGRG1 receptor may represent a novel approach for the treatment of T2D.
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Dunér
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Israa Mohammad
authors.initials: IM
authors.lastname: Al-Amily
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Arvind
authors.initials: A
authors.lastname: Soni
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Asplund
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Fateme
authors.initials: F
authors.lastname: Safi
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Storm
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Amisten
authors.affiliation: Department of Clinical Science (P.D.), Skånes Universitetssjukhus, Division of Experimental Cardiovascular Research; Islet Cell Physiology (I.M.A.-A., A.So., O.A., F.S., P.S., S.A., A.Sa.); Diabetes and Endocrinology (L.G.); University of Lund, 205 02 Sweden; and Department of Neuroscience and Physiology (A.Sa.), Metabolic Research Unit, University of Goteborg, 405 30 Goteborg, Sweden.
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D024061:Collagen Type III / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
chemical_list: C118925:ADGRG1 protein, human; D024061:Collagen Type III; D043562:Receptors, G-Protein-Coupled; D017868:Cyclic AMP-Dependent Protein Kinases