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The endocannabinoid system: a promising target for the management of type 2 diabetes.
Curr Protein Pept Sci. 2009 Feb; 10(1):56-74.CP

Abstract

Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications. Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism. Not only it regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but it also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolic changes. Conversely, rimonabant, the first selective CB(1) receptor antagonist in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in glycated hemoglobin (HbA1c) levels was observed in metformin- or sulfonylurea-treated patients with type 2 diabetes and in drug-naive or insulin-treated diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared to placebo. New trials are supposed to confirm the potential role of rimonabant (and other CB1 neutral antagonists or inverse agonists) in overweight/obese patients with type 2 diabetes and high risk cardiovascular disease.

Authors+Show Affiliations

Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, CHU Sart Tilman, University of Liege, Liege, Belgium. andre.scheen@chu.ulg.ac.be

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19275673

Citation

Scheen, André J.. "The Endocannabinoid System: a Promising Target for the Management of Type 2 Diabetes." Current Protein & Peptide Science, vol. 10, no. 1, 2009, pp. 56-74.
Scheen AJ. The endocannabinoid system: a promising target for the management of type 2 diabetes. Curr Protein Pept Sci. 2009;10(1):56-74.
Scheen, A. J. (2009). The endocannabinoid system: a promising target for the management of type 2 diabetes. Current Protein & Peptide Science, 10(1), 56-74.
Scheen AJ. The Endocannabinoid System: a Promising Target for the Management of Type 2 Diabetes. Curr Protein Pept Sci. 2009;10(1):56-74. PubMed PMID: 19275673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid system: a promising target for the management of type 2 diabetes. A1 - Scheen,André J, PY - 2009/3/12/entrez PY - 2009/3/12/pubmed PY - 2009/4/8/medline SP - 56 EP - 74 JF - Current protein & peptide science JO - Curr. Protein Pept. Sci. VL - 10 IS - 1 N2 - Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications. Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism. Not only it regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but it also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain and associated metabolic changes. Conversely, rimonabant, the first selective CB(1) receptor antagonist in clinical use, has been shown to reduce body weight, waist circumference, triglycerides, blood pressure, insulin resistance and C-reactive protein levels, and to increase HDL cholesterol and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. In addition, a 0.5-0.7% reduction in glycated hemoglobin (HbA1c) levels was observed in metformin- or sulfonylurea-treated patients with type 2 diabetes and in drug-naive or insulin-treated diabetic patients. Almost half of metabolic changes occurred beyond weight loss, in agreement with direct peripheral effects. Rimonabant was generally well-tolerated, but with a slightly higher incidence of depressed mood disorders, anxiety, nausea and dizziness compared to placebo. New trials are supposed to confirm the potential role of rimonabant (and other CB1 neutral antagonists or inverse agonists) in overweight/obese patients with type 2 diabetes and high risk cardiovascular disease. SN - 1389-2037 UR - https://www.unboundmedicine.com/medline/citation/19275673/The_endocannabinoid_system:_a_promising_target_for_the_management_of_type_2_diabetes_ L2 - http://www.eurekaselect.com/83905/article DB - PRIME DP - Unbound Medicine ER -