Activation of cannabinoid CB1 receptors induces glucose intolerance in rats

• Published in: European journal of pharmacology Vol. 531; no. 1-3; pp. 282 - 284
• Main Authors: BERMUDEZ-SIVA, Francisco Javier, SERRANO, Antonia, DIAZ-MOLINA, Francisco Javier, SANCHEZ VERA, Irene, JUAN-PICO, Pablo, NADAL, Angel, FUENTES, Esther, RODRIGUEZ DE FONSECA, Femando
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 15.02.2006
• Subjects: Animals; Arachidonic Acids - pharmacology; Biological and medical sciences; Blood Glucose - metabolism; Cannabinoid Receptor Modulators - pharmacology; Diabetes. Impaired glucose tolerance; Endocannabinoids; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose Intolerance - chemically induced; Glucose Intolerance - physiopathology; Glucose Intolerance - prevention & control; Male; Medical sciences; Pharmacology. Drug treatments; Piperidines - pharmacology; Polyunsaturated Alkamides; Pyrazoles - pharmacology; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - physiology; Endocrinopathy; CB1 cannabinoid receptor; Rat; Glucose intolerance; Arachidonic acid derivatives; Rodentia; Endogenous substance; Cannabinoid; Anandamide; Vertebrata; Mammalia; Animal; Cannabinoid receptor; Impaired glucose tolerance
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.12.016

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.