Regulation of renal tubular glucose reabsorption by Akt2/PKBβ
Akt/PKB is known to regulate the facilitative glucose carrier GLUT4. Nothing is known, however, of the role of Akt/PKB in the regulation of renal epithelial transport. To explore whether Akt2/PKBβ influences the Na+-coupled glucose cotransporter SGLT1, human SGLT1 was expressed in Xenopus laevis oocytes with or without Akt/PKB, and electrogenic glucose transport was determined by dual-electrode voltage clamp. The coexpression of Akt/PKB in SGLT1-expressing oocytes was followed by an increase in glucose-induced currents. To study the functional significance of Akt/PKB-sensitive renal glucose transport, further experiments were performed in gene-targeted mice lacking functional Akt2/PKBβ ( akt2−/−) and in their wild-type littermates ( akt2+/+). Plasma glucose concentration was significantly higher in akt2−/− mice than in akt2+/+ mice but was virtually identical to the plasma glucose concentration in fructose-treated akt2+/+ mice. Urinary glucose excretion was significantly higher in akt2−/− mice compared with akt2+/+ mice with or without fructose treatment. Moreover, the glucose-induced depolarization of proximal tubular cells was significantly smaller in isolated, perfused renal tubules from akt2−/− mice than in those from akt2+/+ mice. In conclusion, Akt2/PKBβ plays a role in the regulation of renal glucose transport.