GLUT2/SLC2A2 is a bi-directional urate transporter.

Recent genetic studies showed an association between solute carrier 2A2 (SLC2A2), which encodes glucose transporter 2 (GLUT2), and serum urate concentrations; however, urate transport activity of GLUT2 has not been studied contrary to its function as a sugar transporter. Here, we hypothesized that GLUT2 acts also as a urate transporter, which led us to conduct cell-based functional analyses using HEK-derived 293A cells. We found that radiolabeled [8-14C]-urate was incorporated into GLUT2-expressing cells more compared to control cells and this elevated cellular activity was almost completely inhibited by GLUT2 inhibitors, demonstrating that GLUT2 is a urate transporter. Regarding the concentration dependence of GLUT2-mediated urate transport, no saturable properties were observed within an experimentally achievable range (0-500 μM), suggesting that GLUT2 mediates the robust transport of urate. Moreover, the GLUT2-mediated urate transport was not inhibited by 10 mM glucose; GLUT2-mediated sugar transport was hardly affected by 500 μM urate. As these concentrations of urate and glucose were relevant to their maximum levels in healthy humans, our results suggest that GLUT2 maintains its urate transport ability under physiological conditions, Furthermore, using a cell-based urate efflux assay system, we successfully demonstrated that urate secretion was accelerated in GLUT2-expressing cells than in control cells. Therefore, GLUT2 may also function as a urate exporter. The present study revealed that GLUT2 is a bi-directional urate transporter. Our findings contribute to a deeper understanding of urate-handling systems in the body. To elucidate the physiological role of GLUT2 as a urate transporter, further studies are required.