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

Dunér, Pontus LU ; Mohammed, Israa LU ; Soni, Arvind LU ; Asplund, Olof LU ; Safi, Fatemeh LU ; Storm, Petter LU ; Groop, Leif LU ; Amisten, Stefan LU and Salehi, S Albert LU (2016) In Journal of Clinical Endocrinology and Metabolism 101(12). p.4637-4645
Abstract

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,... (More)

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.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
101
issue
12
pages
9 pages
publisher
The Endocrine Society
external identifiers
  • scopus:85003550875
  • wos:000390951000016
ISSN
0021-972X
DOI
10.1210/jc.2016-1884
language
English
LU publication?
yes
id
8c156006-fe9b-4ff0-a67c-1642e27f8f62
date added to LUP
2016-12-28 15:55:57
date last changed
2017-09-18 11:33:55
@article{8c156006-fe9b-4ff0-a67c-1642e27f8f62,
  abstract     = {<p>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.</p>},
  author       = {Dunér, Pontus and Mohammed, Israa and Soni, Arvind and Asplund, Olof and Safi, Fatemeh and Storm, Petter and Groop, Leif and Amisten, Stefan and Salehi, S Albert},
  issn         = {0021-972X},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {4637--4645},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Adhesion G protein-coupled receptor G1 (ADGRG1/GPR56) and pancreatic β-cell function},
  url          = {http://dx.doi.org/10.1210/jc.2016-1884},
  volume       = {101},
  year         = {2016},
}