Activation of aryl hydrocarbon receptor stimulates GLUT-mediated glucose transport in human renal proximal tubular cells.

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays a major role in detoxification of xenobiotics. AhR deficiency has been shown to attenuate renal injury induced by diabetes. It is interesting whether the beneficial effect of AhR deficiency on renal injury in diabetes involve in alteration of intracellular glucose in renal tubular cells. The aim of this study was to investigate the effect and mechanism of AhR on glucose uptake into human renal proximal tubular cells. Exposure HK-2 cells, human renal proximal tubular cell line, with omeprazole, an AhR agonist, increased glucose transporter (GLUT)-mediated [ H]-2-Deoxy-D glucose uptake into the cells in concentration-dependent manner. The stimulatory effect of omeprazole was reduced by co-incubation with CH223191, an AhR antagonist. These results indicate that the stimulatory effect of omeprazole on GLUT transport function regards activation of AhR. The kinetic study showed that omeprazole significantly decreased half-maximal transport (K ) but not maximal rate of transport (J ) of GLUT, suggesting that AhR might increase affinity of GLUT-mediated glucose uptake into the cells. In addition, activation of AhR significantly induced cellular level of ROS. Inhibition of ROS using N-acetyl-L-cysteine (NAC) inhibited the stimulatory effect of AhR on GLUT-mediated glucose uptake. These results support that activation of AhR increases GLUT-mediated glucose accumulation via increase in ROS production in human renal proximal tubular cells. Inhibition of AhR might be a target for treatment of high glucose-induced renal injury from diabetes.