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.