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.
(Less)
- author
- 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
- organization
- publishing date
- 2016-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 101
- issue
- 12
- pages
- 9 pages
- publisher
- Oxford University Press
- external identifiers
-
- pmid:27636017
- wos:000390951000016
- scopus:85003550875
- 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
- 2024-11-16 14:16:41
@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 = {{Oxford University Press}},
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}},
doi = {{10.1210/jc.2016-1884}},
volume = {{101}},
year = {{2016}},
}