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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; Persaud, Shanta J.; Baker, David; Alonso, Francisco José; Bermúdez‐Silva, Francisco Javier
- Abstract
Aims: 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. Materials and methods: 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. Results: 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. Conclusions: 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.
- Subjects
CANNABINOIDS; PANCREATIC beta cells; ISLANDS of Langerhans; CYTOKINES; GLUCOSE-regulated proteins
- Publication
Diabetes, Obesity & Metabolism, 2018, Vol 20, Issue 4, p930
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/dom.13180