GPR55: a new promising target for metabolism?

Abstract

GPR55 is a G-protein-coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans. The potential of GPR55 to become a new pharmaceutical target to treat obesity and type 2 diabetes, as well as the foreseeing difficulties are also discussed.

LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling

“…As a parallel investigative strategy we studied the requirement of GPR55 for insulin secretion induced by Abn‐CBD, a cannabinoid that is reported to be at least 10‐fold more selective for GPR55 than for CB1 or CB2 . It has previously been demonstrated that Abn‐CBD increases insulin secretion from BRIN‐BD11 insulin‐secreting cells and mouse islets .…”

“…The requirement for GPR55 to mediate the stimulatory effects of 1 nM and 0.1 μM LH‐21 on insulin secretion was unexpected, given that LH‐21 is considered to be an antagonist or inverse agonist at CB1. We therefore explored the effects of LH‐21 and Abn‐CBD on changes in [Ca 2+ ] i , since it is known that GPR55 couples to G q and Gα 13 pathways that regulate Ca 2+ levels.…”

“…17 As a parallel investigative strategy we studied the requirement of GPR55 for insulin secretion induced by Abn-CBD, a cannabinoid that is reported to be at least 10-fold more selective for GPR55 than for CB1 or CB2. 16 It has previously been demonstrated that Abn-CBD increases insulin secretion from BRIN-BD11 insulin-secreting cells and mouse islets. 11 In the present study we confirmed that Abn-CBD potentiated glucose-induced insulin secretion from mouse islets and we also demonstrated, for the first time, that it has similar stimulatory effects in human islets.…”

“…CB1 and CB2 are the canonical receptors for cannabinoids, whilst another GPCR, GPR55, which has low sequence homology with CB1 and CB2 1 and lacks the typical "cannabinoid binding pocket," 2 is also activated by some cannabinoids. [3][4][5][6][7][8][9] CB1 and GPR55 have in common an abundant expression in the central nervous system and metabolic tissues and a proposed role in energy balance, [10][11][12][13][14][15][16] that may be secondary to their regulation of insulin secretion. 10,11,13,14,17 We, and others, have shown that CB1 and GPR55 activation in isolated rodent and human islets is associated with insulinotropic properties, 10,11,13,14,18 although a shared consensus in the scientific community has still not been reached with respect to the role of CB1 receptors in islets.…”

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study

“…Studies in rodent showed that GPR55 is present in hippocampus, thalamus, forebrain, frontal cortex, hypothalamus, cerebellum and striatum [64]. There is increasing evidence of co-expression and cross-talk between cannabinoid receptors supporting the notion that ligands binding to the CB 1 receptor could influence the response to ligands acting through GPR55, and vice versa [65].…”