Antidiabetic effects of sub-chronic administration of the cannabinoid receptor (CB1) antagonist, AM251, in obese diabetic (ob/ob) mice

European Journal of Pharmacology
Nigel IrwinPeter R Flatt

Abstract

Recent research suggests that cannabinoid CB1 receptor antagonism reduces appetite and body weight gain. The present study was designed to assess the sub-chronic effects of the selective cannabinoid CB1 receptor antagonist, AM251 (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide), in young ob/ob mice. Pair-fed animals were used as additional controls. Daily injection of AM251 (6 mg/kg body weight) for 18 days significantly (P<0.05) decreased daily and 18-day cumulative food intake. The corresponding body weight change did not achieve significance and values were not different from pair-fed mice. Non-fasting plasma glucose was decreased (P<0.05) from day 10 onwards by AM251 treatment. The glycaemic response to intraperitoneal glucose was correspondingly improved (P<0.05) in AM251 treated mice. In keeping with this, insulin sensitivity was enhanced (P<0.05) compared to controls. Furthermore, adipose mRNA levels of acetyl-CoA carboxylase 1 were significantly (P<0.05) reduced by 18 days AM251 treatment. There were no differences in either non-fasting or glucose-stimulated insulin release. Pair-feeding had broadly similar metabolic effects to AM251 treatment apart from increased (P<0.01) ...Continue Reading

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Citations

Oct 17, 2009·American Journal of Therapeutics·Zafar H Israili
Nov 9, 2010·Pharmacology, Biochemistry, and Behavior·Nina L ClunyKeith A Sharkey
Apr 24, 2015·Veterinary Research Communications·Abbas AlizadehShahin Hassanpour
Feb 25, 2011·Diabetes·Wook KimJosephine M Egan
Aug 13, 2013·Metabolism: Clinical and Experimental·Ikram MerrounMaría López-Jurado
Mar 23, 2017·The Journal of Biological Chemistry·Dipanjan ChandaDietbert Neumann
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Feb 12, 2011·Current Opinion in Endocrinology, Diabetes, and Obesity·Máire E Doyle

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