Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice.

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Abstract

BACKGROUND AND PURPOSE: G-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.EXPERIMENTAL APPROACH: Insulin secretion and changes in intracellular Ca2+ and cAMP in response to glucose and a range of GPR55 agonists (endogenous ligands (OEA, PEA), chemically synthetic CBD analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)) were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localisation by double-staining immunohistochemistry and in vivo effects assessed in mice.KEY RESULTS: The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67% at 10-4 mol/l (p
LanguageEnglish
Pages978-990
JournalBritish Journal of Pharmacology
Volume170
Issue number5
DOIs
Publication statusPublished - 28 Aug 2013

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rimonabant
Islets of Langerhans
Hypoglycemic Agents
Insulin
Ligands
Lipids
Glucose
Endocannabinoids
Cannabinoids
G-Protein-Coupled Receptors
Homeostasis
Immunohistochemistry
Staining and Labeling
AM 251

Cite this

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title = "Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice.",
abstract = "BACKGROUND AND PURPOSE: G-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.EXPERIMENTAL APPROACH: Insulin secretion and changes in intracellular Ca2+ and cAMP in response to glucose and a range of GPR55 agonists (endogenous ligands (OEA, PEA), chemically synthetic CBD analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)) were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localisation by double-staining immunohistochemistry and in vivo effects assessed in mice.KEY RESULTS: The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67{\%} at 10-4 mol/l (p",
author = "Aine McKillop and BM Moran and Yasser Abdel-Wahab and Peter Flatt",
year = "2013",
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TY - JOUR

T1 - Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice.

AU - McKillop, Aine

AU - Moran, BM

AU - Abdel-Wahab, Yasser

AU - Flatt, Peter

PY - 2013/8/28

Y1 - 2013/8/28

N2 - BACKGROUND AND PURPOSE: G-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.EXPERIMENTAL APPROACH: Insulin secretion and changes in intracellular Ca2+ and cAMP in response to glucose and a range of GPR55 agonists (endogenous ligands (OEA, PEA), chemically synthetic CBD analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)) were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localisation by double-staining immunohistochemistry and in vivo effects assessed in mice.KEY RESULTS: The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67% at 10-4 mol/l (p

AB - BACKGROUND AND PURPOSE: G-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.EXPERIMENTAL APPROACH: Insulin secretion and changes in intracellular Ca2+ and cAMP in response to glucose and a range of GPR55 agonists (endogenous ligands (OEA, PEA), chemically synthetic CBD analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)) were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localisation by double-staining immunohistochemistry and in vivo effects assessed in mice.KEY RESULTS: The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67% at 10-4 mol/l (p

U2 - 10.1111/bph.12356

DO - 10.1111/bph.12356

M3 - Article

VL - 170

SP - 978

EP - 990

JO - British Journal of Pharmacology

T2 - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 5

ER -