SGLT2 is a sodium-coupled glucose cotransporter localized at the apical membrane of renal proximal tubule that uptakes glucose from urine into the cells in a Na⁺-dependent manner. Although SGLT2 inhibitors are clinically used to reduce blood sugar, they exhibit uric acid lowering action at the same time. However, its molecular mechanism is still unknown. This study aims to elucidate its molecular mechanism behind the interaction between SGLT2 inhibitor and renal tubular transporters. cRNAs of URAT1 (SLC22A12), OAT10 (SLC22A13) and URATv1 (SLC2A9) were injected into Xenopus oocytes. 2-3 days later, we measured urate and glucose transport activities, the inhibition by glucose and SGLT2 inhibitor tofogliflozin (tofo) on uric acid transport, and the inhibition by urate on glucose transport. Urate transport by three was not inhibited by glucose. It was newly found that glucose is significantly transported by all, but since its transport inhibition by urate was not observed, any transporter has different substrate recognition sites for glucose and uric acid. In addition, urate transport by three was not inhibited by tofo.
Thus, urate-lowering action by SGLT2 inhibitor was considered unlikely to be due to the interaction with the existing major renal tubular urate transporter.