Lack of a Significant Effect of Cannabinoids upon the Uptake of 2-Deoxy-D-Glucose by Caco-2 Cells

Abstract

The endogenous cannabinoid system plays a role in the regulation of energy homeostasis acting through central pathways, and its dysregulation may be implicated in the pathogenesis of obesity. Recent evidence is accumulating showing that the endogenous cannabinoid system is also present in peripheral tissues. The aim of this work was to investigate the effect of cannabinoids upon the intestinal absorption of glucose. For this, we investigated the effect of some cannabinoid receptor agonists and antagonists upon the apical uptake of ³H-2-deoxy-D-glucose by the human intestinal epithelial Caco-2 cells. Uptake of a low concentration of ³H-2-deoxy-D-glucose (1 µmol/l) was both cytochalasin B- and phloridzin-sensitive. The maximal inhibition obtained with each of these inhibitors was 50%, and their effect was not cumulative. On the other hand, uptake of a high concentration of ³H-2-deoxy-D-glucose (20 mmol/l) was partially inhibited by cytochalasin B (±20%) and phloridzin had no effect. We verified that neither the cannabinoid receptor agonists [tetrahydrocannabinol (1–10 µmol/l), anandamide (0.1–10 µmol/l) and CP 55,940 (5 nmol/l to 1 µmol/l)], nor the specific CB₁ and CB₂ antagonists [AM251 (10–500 nmol/l) and AM630 (50 nmol/l to 1 µmol/l), respectively] had a significant effect upon ³H-2-deoxy-D-glucose uptake by Caco-2 cells. This was true for both the uptake of a low (1 µmol/l) and of a high (20 mmol/l) concentration of ³H-2-deoxy-D-glucose. From these results, we may hypothesize that cannabinoids do not interfere with the intestinal GLUT2-mediated apical uptake of glucose.