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Title: LH-21 and abnormal cannabidiol improve β-cell function in isolated human and mouse islets through GPR55-dependent and -independent signalling.
Authors: Ruz-Maldonado, Inmaculada
Pingitore, Attilio
Liu, Bo
Atanes, Patricio
Huang, Guo Cai
Baker, David
Alonso, Francisco José
Bermúdez-Silva, Francisco Javier
Persaud, Shanta J
Keywords: cannabinoids;insulin secretion;islets;proliferation;β-cell function
metadata.dc.subject.mesh: Adult
Cells, Cultured
Insulin-Secreting Cells
Islets of Langerhans
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Receptors, Cannabinoid
Receptors, G-Protein-Coupled
Signal Transduction
Issue Date: 10-Jan-2018
Abstract: To examine the effects of Abn-CBD (GPR55 agonist) and LH-21 (CB1 antagonist) on human and mouse islet function, and to determine signalling via GPR55 using islets from GPR55-/- mice. Islets isolated from human organ donors and mice were incubated in the absence or presence of Abn-CBD or LH-21, and insulin secretion, [Ca2+ ]i, cAMP, apoptosis, β-cell proliferation and CREB and AKT phosphorylation were examined using standard techniques. Abn-CBD potentiated glucose-stimulated insulin secretion and elevated [Ca2+ ]i in human islets and islets from both GPR55+/+ and GPR55-/- mice. LH-21 also increased insulin secretion and [Ca2+ ]i in human islets and GPR55+/+ mouse islets, but concentrations of LH-21 up to 0.1 μM were ineffective in islets from GPR55-/- mice. Neither ligand affected basal insulin secretion or islet cAMP levels. Abn-CBD and LH-21 reduced cytokine-induced apoptosis in human islets and GPR55+/+ mouse islets, and these effects were suppressed after GPR55 deletion. They also increased β-cell proliferation: the effects of Abn-CBD were preserved in islets from GPR55-/- mice, while those of LH-21 were abolished. Abn-CBD and LH-21 increased AKT phosphorylation in mouse and human islets. This study showed that Abn-CBD and LH-21 improve human and mouse islet β-cell function and viability. Use of islets from GPR55-/- mice suggests that designation of Abn-CBD and LH-21 as a GPR55 agonist and a CB1 antagonist, should be revised.
metadata.dc.identifier.doi: 10.1111/dom.13180
Appears in Collections:Producción 2020

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