CRISPR/Cas9 gene editing demonstrates metabolic importance of GPR55 in the modulation of GIP release and pancreatic beta cell function

•CRISPR/Cas9 gene editing has determined the specificity of a number of endogenous and synthetic cannabinoid agonists.•The CRISPR tool has determined GPR55-dependent insulin secretion through Gαq activation and intracellular Ca2+ modulation.•GPR55 agonists act as insulinotropic and glucose-lowering agents for the benefit of type 2 diabetes, mediated partly by enhanced GIP and GLP-1 secretion.•Combinational therapy using a DPP-IV inhibitor enhanced the glucose lowering capabilities of the cannabinoid compounds.