Inhibitors of cannabinoid receptors and glucose metabolism.
OBJECTIVE
Abdominal obesity is closely related to type 2 diabetes and overactivity of the endocannabinoid system. The present review aims at evaluating the role of endocannabinoid system in glucose dysregulation and the effects of cannabinoid 1 receptor blockade on glucose metabolism in both animal models and overweight/obese humans, especially with type 2 diabetes.


RESULTS
Cannabinoid 1 receptors have been identified not only in the brain, but also in the adipose tissue, the gut, the liver, the skeletal muscle and even the pancreas, all organs playing a key role in glucose metabolism and type 2 diabetes. Rimonabant, the first selective cannabinoid 1 receptor blocker in clinical use, has been shown to reduce body weight, waist circumference, glycated haemoglobin, triglycerides, insulin resistance index, and to increase HDL cholesterol and adiponectin concentrations in patients with type 2 diabetes, confirming data on nondiabetic overweight/obese patients. Almost half of the metabolic changes, including glycated haemoglobin reduction, could not be explained by weight loss, in agreement with direct peripheral effects.


CONCLUSIONS
Cannabinoid 1 blockade reduces food intake and body weight and improves metabolic regulation beyond just weight loss. Because of its positive effect on glucose metabolism, rimonabant deserves consideration in the treatment of overweight/obese patients with type 2 diabetes.
Scheen
André J
AJ
Division of Diabetes, Nutrition and Metabolic Disorders, CHU Sart Tilman, University of Liège, Liège, Belgium. andre.scheen@chu.ulg.ac.be
Paquot
Nicolas
N
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000502:physiology; D000077285:Rimonabant
D001786:Blood Glucose; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; D000077285:Rimonabant