Adhesion G Protein-Coupled Receptor G1 (ADGRG1/GPR56) and Pancreatic ß-Cell Function.
J Clin Endocrinol Metab
; 101(12): 4637-4645, 2016 12.
Article
en En
| MEDLINE
| ID: mdl-27636017
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 ß-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 ß-cell proliferation, apoptosis, and insulin secretion in human and mouse islets and in INS-1 cells. MAIN OUTCOMEMEASURES:
Changes in ß-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 in human islets strongly correlates with genes important for ß-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 ß-cell function via activation of the cAMP/protein kinase A pathway, suppression of RhoA and caspase-3 activity, increased ß-cell viability, and proliferation were abolished when ADGRG1 was down-regulated in ß-cells.CONCLUSIONS:
We demonstrate a mechanistic link between ADGRG1 expression and ß-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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Proteínas Quinasas Dependientes de AMP Cíclico
/
Colágeno Tipo III
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Receptores Acoplados a Proteínas G
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Diabetes Mellitus Tipo 2
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Células Secretoras de Insulina
/
Hiperglucemia
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2016
Tipo del documento:
Article