title: A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans.
abstract: The cannabinoid CB1 receptor is a well-known player in energy homeostasis and its specific antagonism has been used in clinical practice for the treatment of obesity. The G protein-coupled receptor GPR55 has been recently proposed as a new cannabinoid receptor and, by contrast, its pharmacology is still enigmatic and its physiological role is largely unexplored, with no reports investigating its putative role in metabolism. Thus, we aim to investigate in rats the presence, distribution and putative physiological role of GPR55 in a key metabolic tissue, the endocrine pancreas. We found high Gpr55 mRNA content in pancreatic islets and considerable protein distribution in insulin-secreting β-cells. Activation of GPR55 by the agonist O-1602 increased calcium transients (P<0.01) and insulin secretion (P<0.001) stimulated by glucose. This latter effect was blunted in Gpr55 KO mice suggesting that O-1602 is acting, at least in part, through GPR55. Indeed, acute in vivo experiments showed that GPR55 activation increases glucose tolerance (P<0.05) and plasma insulin levels (P<0.05), suggesting an in vivo physiological relevance of GPR55 systemic stimulation. Taken together, these results reveal the expression of GPR55 receptors in the endocrine pancreas as well as its function at stimulus-secretion coupling of insulin secretion, suggesting a role in glucose homeostasis. In this context, it may also represent a new target for consideration in the management of type 2 diabetes and related diseases.
authors: Fundación IMABIS, Hospital Carlos Haya de Málaga, Laboratorio de Medicina Regenerativa, Pabellón de Gobierno, sótano, Málaga, Spain.
authors: Silvana Y
authors: SY
authors: Romero-Zerbo
authors: Alex
authors: A
authors: Rafacho
authors: Adenis
authors: A
authors: Díaz-Arteaga
authors: Juan
authors: J
authors: Suárez
authors: Ivan
authors: I
authors: Quesada
authors: Mónica
authors: M
authors: Imbernon
authors: Ruth A
authors: RA
authors: Ross
authors: Carlos
authors: C
authors: Dieguez
authors: Fernando
authors: F
authors: Rodríguez de Fonseca
authors: Rubén
authors: R
authors: Nogueiras
authors: Angel
authors: A
authors: Nadal
authors: Francisco J
authors: FJ
authors: Bermúdez-Silva
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002185:Cannabidiol / Q000031:analogs & derivatives; D002186:Cannabinoids / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002186:Cannabinoids; D003510:Cyclohexanes; C526692:GPR55 protein, mouse; D007328:Insulin; D043882:Receptors, Cannabinoid; D012118:Resorcinols; D002185:Cannabidiol; C568537:O-1602 compound; D005947:Glucose; D002118:Calcium