Cannabinoids inhibit insulin secretion and cytosolic Ca2+ oscillation in islet beta-cells via CB1 receptors.
Obesity is the main risk factor for the development of metabolic syndrome. Endogenous cannabinoids act on the cannabinoid type 1 (CB1) receptor, a GPCR, and stimulate appetite via central and peripheral actions, while blockade of CB1 receptor reduces body weight in humans. In this study, we aimed to explore a role of the peripheral endocannabinoid system in insulin secretion, which could be important in the metabolic effects of the cannabinoid-CB1 system. We found that mRNA for CB1 receptor, but not CB2 receptor, was expressed in mouse pancreatic islets using RT-PCR. Immunohistochemical study revealed that CB1 receptor was expressed in beta-cells. Furthermore, anandamide and a CB1 agonist, arachidonylcyclopropylamide (ACPA), inhibited glucose-induced insulin secretion from mouse pancreatic islets. Both anandamide and ACPA inhibited glucose-induced cytosolic Ca(2+) oscillation in mouse pancreatic beta-cells. These results demonstrate a novel peripheral action of cannabinoids to inhibit insulin secretion via CB1 receptors.
Nakata
Masanori
M
Department of Physiology, Division of Integrative Physiology, Jichi Medical School, School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi, 329-0498, Japan.
Yada
Toshihiko
T
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002186:Cannabinoids / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism*; D063388:Endocannabinoids; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D007328:Insulin; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D005947:Glucose; D002118:Calcium; C078814:anandamide