title: Expression and function of monoacylglycerol lipase in mouse β-cells and human islets of Langerhans.
abstract: Elements of the endocannabinoid system (ECS) are expressed by islet endocrine cells and activation of CB1 and CB2 cannabinoid receptors regulates insulin secretion from mouse and human β-cells. The current study aimed to investigate the expression and function, in mouse and human β-cells, of monoacylglycerol lipase (MGL), an enzyme that facilitates degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). We found that MGL mRNA is expressed by MIN6 β-cells, mouse islets, human islets and enriched human islet β-cells, and immunohistochemistry indicated that MGL localisation in human islets is consistent with its expression by some β- and -α-cells. Blockade of MGL activity with the pharmacological inhibitor URB602 led to increased [Ca(2+)](i )and enhanced insulin secretion from MIN6 β-cells, and MGL inhibition also elevated insulin and glucagon secretion from isolated human islets in vitro. These data imply a stimulatory role for endogenous 2-AG in islets that is amplified when its degradation is blocked.
authors: Diabetes Research Group, Division of Diabetes & Nutritional Sciences, King's College London, London, UK.
authors: Chen
authors: C
authors: Li
authors: Alonso
authors: A
authors: Vilches-Flores
authors: Min
authors: M
authors: Zhao
authors: Stephanie A
authors: SA
authors: Amiel
authors: Peter M
authors: PM
authors: Jones
authors: Shanta J
authors: SJ
authors: Persaud
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D063388:Endocannabinoids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005934:Glucagon / Q000378:metabolism; D005989:Glycerides / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008994:Monoacylglycerol Lipases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D001713:Biphenyl Compounds; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D007328:Insulin; C501835:URB602; C094503:glyceryl 2-arachidonate; D005934:Glucagon; D008994:Monoacylglycerol Lipases; D002118:Calcium