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.
Kempe
D S
DS
Department of Physiology, University of Tübingen, Tübingen, Germany.
Ackermann
T F
TF
Boini
K M
KM
Klaus
F
F
Umbach
A T
AT
Dërmaku-Sopjani
M
M
Judenhofer
M S
MS
Pichler
B J
BJ
Capuano
P
P
Stange
G
G
Wagner
C A
CA
Birnbaum
M J
MJ
Pearce
D
D
Föller
M
M
Lang
F
F
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