[en] Endocannabinoid system is overactivated in individuals with abdominal obesity. CBI receptors, first individualized in the brain, are also expressed in the adipocyte, the skeletal muscle, the liver, the gut, and the pancreas. Their blockade improves glucose tolerance and lipid profile, thanks increased insulin sensitivity and adiponectin levels. Rimonabant, a selective antagonist of CBI receptors, improves glucose control in patients with type 2 diabetes, treated with diet alone, metformin, sulfonylurea or insulin, while it also reduces body weight and other risk factors. Ongoing studies aim at further demonstrating the potential of rimonabant in the management of type 2 diabetes, in the prevention of type 2 diabetes and in the protection against cardiovascular complications in (diabetic) patients with abdominal obesity.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Paquot, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Van Gaal, Luc F
Language :
French
Title :
Inhibition des recepteurs CB1 et metabolisme du glucose: rimonabant dans le diabete de type 2.
Alternative titles :
[fr] CB1 receptor inhibition and glucose metabolism: role of rimonabant in type 2 diabetes
Scheen AJ. Obesity and diabetes. In : The management of obesity and related disorders. London : Ed : Kopelman PG, Martin Dunitz Ltd, 2001;11-44.
Scheen AJ. Diabetes, obesity, and metabolic syndrome. In : Nutrient-drug interactions (Ed : Meckling KA). Boca Raton, FL, US, CRC Press Taylor & Francis, 2007; 1-30.
Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006;444:875-80.
Scheen AJ. Current management strategies for co-existing diabetes mellitus and obesity. Drugs 2003;63:1165-84.
Gasde P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008;358:580-91.
Alexander SPH, Kendall DA. The complications of promiscuity : Endocannabinoid action and metabolism. Br J Pharmacol 2007;152:602-23.
Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006;27:73-100.
** Di Marzo V. The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 2008;51:1356-67.
Bermudez-Silva FJ, Suarez J, Baixeras E, et al. Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia 2008;51:476-87.
Cote M, Matias I, Lemieux I, et al. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obesity 2007;31:692-9.
* Scheen AJ, Van Gaal LG, Després JP, et al. Le rimonabant améliore le profil de risque cardio-métabolique chez le sujet obèse ou en surpoids : synthèse des études «RIO». Rev Med Suisse 2006;2:1916-23.
Van Gaal LF, Pi-Sunyer X, Després JP, et al. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients : Pooled 1-year data from the RIO program. Diabetes Care 2008;31(Suppl. 2):S229-40.
Scheen AJ. CB1 receptor blockade and its impact on cardiometabolic risk factors : Overview of the RIO programme with rimonabant. J Neuroendocrinol 2008;20(Suppl. 1):139-46.
Scheen AJ, Van Gaal LF. Rimonabant (Acomplia). Premier antagoniste des récepteurs CBI du système endocannabinoïde. Rev Med Liège 2008;63:50-5.
* Lafontan M, Piazza PV, Girard J. Effects of CB1 antagonist on the control of metabolic functions in obese type 2 diabetic patients. Diabetes Metab 2007;33:85-95.
* Scheen AJ, Paquot N. Inhibitors of cannabinoid receptors and glucose metabolism. Curr Opin Clin Nutr Metab Care 2008;11:505-11.
Scheen AJ. Cannabinoid-1 receptor antagonists in type-2 diabetes. Best Pract Res Clin Endocrinol Metab 2007;21:535-53.
Scheen AJ. Endocannabinoid system, a new target for the management of type 2 diabetes. Curr Protein Pept Sci 2008;in press.
Després JP, Golay A, Sjöström L ; rimonabant in obesity-lipids study group. Effects on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005;353:2121-34.
Guerre-Millo M. Adiponectin : An update. Diabetes Metab 2008;34:12-8.
Osei-Hyiaman D, DePetrillo M, Pacher P, et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005;115:1298-305.
Luyckx FH, Scheen AJ, Lefèbvre PJ. Non-alcoholic steatohepatitis : Association with obesity and insulin resistance, and influence of weight loss. Diabetes Metab 2000;26:98-106.
Liu YL, Connoiey IP,Wilson CA, Stock MJ. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes Retat Metab Disord 2005;29:183-7.
Cavuoto P, McAinch AJ, Hatzinikolas G, et al. Effects of cannabinoid receptors on skeletal muscle oxidative pathways. Mol Cell Endocrinol 2007;267:63-9.
Scheen A,Van Gaal L, Rio-Europe study group. Long-term efficacy of rimonabant in improving glucose tolerance in overweight/obese non-diabetic patients : 2-year results from Rio-Europe (abstract). Diabetes 2008;57(Suppl. 1):A31.
Scheen AJ. Evaluation de l'insulinosécrétion et de l'insulinosensibilité chez l'homme. Thérapie 2007;62:311-8.
Nakata M, Yada T. Cannabinoids inhibit insulin secretion and cytosolic Ca2+ oscillation in islet ,-cells via CB1 receptors. Regul Pept 2008;145:49-53.
Bermudez-Silva FJ, Serrano A, Diaz-Molina FJ, et al. Activation of cannabinoid CB1 receptors induces glucose intolerance in rats. Eur J Pharmacol 2006;531:282-4.
Bermudez-Silva FJ, Suarez J, Sanchez Vera I, et al. Role of cannabinoid CB2 receptors in glucose homeostasis in rats. Eur J Pharmacol 2007;565:207-11.
** Scheen AJ, Finer N, Hollander P, et al for the Rio-Diabetes study group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes : A randomised controlled study. Lancet 2006;368:1660-72.
Rosenstock J, Iranmanesh A, Hollander PA. Improved glycemic control with weight loss plus beneficial effects on atherogenic dyslipidemia with rimonabant in drug-naïve type 2 diabetes : The SERENADE trial (abstract). Diabetes 2007;56(Suppl. 1):A49-50.
Hollander PA, Amod A, Litwak LE. Rimonabant improves glycemic control in insulin-treated type 2 diabetes : The ARPEGGIO trial (abstract). Diabetes 2008;57(Suppl. 1):A95.
* Nissen SE, Nicholls SJ, Wolski K, et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease. The STRADIVARIUS randomized controlled trial. JAMA 2008;299:1547-60.
* Van Gaal LF, Scheen AJ, Rissanen AM, et al. Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors : 2-year results from the Rio-Europe study. Eur Heart J 2008;29:1761-71.
Scheen AJ. Antidiabetic agents in patients with mild dysglycaemia : Prevention or early treatment of type 2 diabetes? Diabetes Metab 2007;33:3-12.
CRESCENDO. www.clinicaltrials.gov/ct/show/NCT00263042?order=2. Accessed February 1, 2007.
