Regulation of renal tubular glucose reabsorption by Akt2/PKBβ

• Published in: American journal of physiology. Renal physiology Vol. 298; no. 5; p. F1113
• Main Authors: Kempe, Daniela S, Siraskar, Gulab, Fröhlich, Henning, Umbach, Anja T, Stübs, Michael, Weiss, Florian, Ackermann, Teresa F, Völkl, Harald, Birnbaum, Morris J, Pearce, David, Föller, Michael, Lang, Florian
• Format: Journal Article
• Language: English
• Published: United States 01-05-2010
• Subjects: Absorption; Animals; Female; Glucose - metabolism; Humans; Kidney Tubules, Proximal - metabolism; Mice; Mice, Knockout; Models, Animal; Oocytes - cytology; Oocytes - metabolism; Patch-Clamp Techniques; Proto-Oncogene Proteins c-akt - deficiency; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Sodium-Glucose Transporter 1 - metabolism; Xenopus laevis
• ISSN: 1522-1466
• DOI: 10.1152/ajprenal.00592.2009

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.