Activation of cannabinoid CB1 receptors induces glucose intolerance in rats.

Recent reports have described the presence of cannabinoid CB1 receptors in pancreatic islets. Here we show that administration of the endogenous cannabinoid anandamide or the selective cannabinoid CB1 receptor agonist Arachidonyl-2'-chloroethylamide (ACEA) results in glucose intolerance after a glucose load. This effect is reversed by the selective cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). These results suggest that targeting cannabinoid CB1 receptors may serve as new therapeutic alternatives for metabolic disorders such as diabetes.