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.
Kempe
Daniela S
DS
Department of Physiology, University of Tübingen, Tübingen, Germany.
Siraskar
Gulab
G
Fröhlich
Henning
H
Umbach
Anja T
AT
Stübs
Michael
M
Weiss
Florian
F
Ackermann
Teresa F
TF
Völkl
Harald
H
Birnbaum
Morris J
MJ
Pearce
David
D
Föller
Michael
M
Lang
Florian
F
D000042:Absorption; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D014982:Xenopus laevis
C495674:SLC5A1 protein, human; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose