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The effect of cannabinoids on the uptake of 2‐deoxy‐D‐glucose by Caco‐2 cells

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. 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, by investigating the effect of cannabinoid receptor agonists and antagonists upon the apical uptake of 3H‐2‐deoxy‐D‐glucose (3H‐DG) by human intestinal epithelial Caco‐2 cells. Uptake of 1 μM3H‐DG was both cytochalasin B‐ and phloridzin‐sensitive (±50% inhibition observed with each of these drugs), and their effect was not cumulative. On the other hand, uptake of 20 mM 3H‐DG was partially inhibited by cytochalasin B (±20%) and phloridzin had no effect. We verified that neither the cannabinoid receptor agonists THC (1–10 μM), anandamide (0.1–10 μM) and CP 55,940 (5 nM‐1 μM), nor the specific CB‐1 and CB‐2 antagonists (AM251 (10‐500 nM) and AM630 (50 nM‐1 μM), respectively) had a significant effect upon 3H‐DG uptake by Caco‐2 cells. This was true for both uptake of the low and high concentration of 3H‐DG. So, we hypothesize that cannabinoids do not interfere with the GLUT2‐mediated intestinal apical uptake of glucose. Supported by FCT (PTDC/SAU‐FCF/67805/2006).