Electrogenic characteristics of the facilitative glucose transporter GLUT12

GLUT12 belongs to the class III of the facilitative glucose transporters family SLC2A. In the present work, we have cloned and studied GLUT12 transport mechanism and shown for the first time electrogenic properties. GLUT12 was expressed in Xenopus laevis oocytes. Kinetic parameters were obtained by uptake assays while electrogenic properties were investigated using the two‐electrode voltage‐clamp technique. Glucose and 3‐O‐methylglucose (5–100 mM) induced inward currents in the presence and absence of sodium that were of similar magnitude, but did not saturate. Moreover, in the absence of sugar there was a Na + ‐leak current. Sodium in the medium induced a 2‐fold increase in the maximal transport rate of 3‐O‐methylglucose uptake while a 3‐fold decrease in the affinity (K 0.5 of 7.5 mM vs. 24.9 mM). The increase of potassium in the medium (from 25 to 100 mM) inhibited both membrane depolarization and sugar uptake. Sorbitol, which is not a GLUT12 substrate, also induced inward current, while the GLUT inhibitor genistein, inhibited glucose uptake but increased glucose‐induced depolarization. In summary, sugars induce ion movement trough GLUT12 and Na + and K + seem to be involved in the transport mechanism, but transport and ion movements are uncoupled, which suggest a substrate‐gated ion channel activity for GLUT‐12, in which Cl − could be involved. This work was supported by Fundación Marcelino Botín.