title: Acute activation of cannabinoid receptors by anandamide reduces gastrointestinal motility and improves postprandial glycemia in mice.
abstract: The endocannabinoid system (ECS) is associated with an alteration of glucose homeostasis dependent on cannabinoid receptor-1 (CB1R) activation. However, very little information is available concerning the consequences of ECS activation on intestinal glucose absorption. Mice were injected intraperitoneally with anandamide, an endocannabinoid binding both CB1R and CB2R. We measured plasma glucose and xylose appearance after oral loading, gastrointestinal motility, and glucose transepithelial transport using the everted sac method. Anandamide improved hyperglycemia after oral glucose charge whereas glucose clearance and insulin sensitivity were impaired, pointing out some gastrointestinal events. Plasma xylose appearance was delayed in association with a strong decrease in gastrointestinal transit, while anandamide did not alter transporter-mediated glucose absorption. Interestingly, transit was nearly normalized by coinjection of SR141716 and AM630 (CB1R and CB2R antagonist, respectively), and AM630 also reduced the delay of plasma glucose appearance induced by anandamide. When gastric emptying was bypassed by direct glucose administration in the duodenum, anandamide still reduced plasma glucose appearance in wild-type but not in CB1R(-/-) mice. In conclusion, our findings demonstrated that acute activation of intestinal ECS reduced postprandial glycemia independently on intestinal glucose transport but rather inhibiting gastric emptying and small intestine motility and strongly suggest the involvement of both CB1R and CB2R.
authors.affiliation: INSERM 866, Team Pathophysiology of Dyslipidemia, University of Burgundy, Dijon, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Troy-Fioramonti
authors.affiliation: INSERM 866, Team Pathophysiology of Dyslipidemia, University of Burgundy, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Demizieux
authors.affiliation: INSERM 866, Team Pathophysiology of Dyslipidemia, University of Burgundy, Dijon, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Gresti
authors.affiliation: INSERM 866, Team Pathophysiology of Dyslipidemia, University of Burgundy, Dijon, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Muller
authors.affiliation: INSERM 866, Team Pathophysiology of Dyslipidemia, University of Burgundy, Dijon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.affiliation: INSERM 866, Team Pathophysiology of Dyslipidemia, University of Burgundy, Dijon, France pascal.degrace@u-bourgogne.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Degrace
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D063388:Endocannabinoids / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006943:Hyperglycemia / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D019518:Postprandial Period; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077285:Rimonabant
chemical_list: D001095:Arachidonic Acids; D001786:Blood Glucose; D063388:Endocannabinoids; D007211:Indoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D000077285:Rimonabant; C094023:iodopravadoline; C078814:anandamide