Akt2/PKBbeta-sensitive regulation of renal phosphate transport.
OBJECTIVE
The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport.


METHODS
The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockout mice (akt2(-/-)) and corresponding wild-type mice (akt2(+/+)). Transporter protein abundance was determined using Western blotting and phosphate transport by (32)P uptake into brush border membrane vesicles.


RESULTS
The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [micromol per 24 h per g BW] was higher by 91% in akt2(-/-) than in akt2(+/+) mice. The phosphaturia of akt2(-/-) mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D(3) concentration (by 46%). Moreover, fractional renal Ca(2+) excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2(-/-) mice.


CONCLUSIONS
Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.
Department of Physiology, University of Tübingen, Tübingen, Germany.
D S
DS
Kempe
T F
TF
Ackermann
K M
KM
Boini
F
F
Klaus
A T
AT
Umbach
M
M
Dërmaku-Sopjani
M S
MS
Judenhofer
B J
BJ
Pichler
P
P
Capuano
G
G
Stange
C A
CA
Wagner
M J
MJ
Birnbaum
D
D
Pearce
M
M
Föller
F
F
Lang
D000818:Animals; D001692:Biological Transport; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D002113:Calcification, Physiologic; D002117:Calcitriol / Q000097:blood; D005260:Female; D006706:Homeostasis; D007015:Hypophosphatemia, Familial / Q000201:enzymology / Q000235:genetics; D007684:Kidney Tubules / Q000201:enzymology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D008871:Microvilli / Q000201:enzymology; D010281:Parathyroid Hormone / Q000097:blood; D018408:Patch-Clamp Techniques; D010710:Phosphates / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D015415:Biomarkers; D010281:Parathyroid Hormone; D010710:Phosphates; C493555:Slc34a1 protein, mouse; C493556:Slc34a1 protein, rat; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D012964:Sodium; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D002117:Calcitriol