Akt2/PKBbeta-sensitive regulation of renal phosphate transport

Acta Physiol (Oxf). 2010 Sep;200(1):75-85. doi: 10.1111/j.1748-1716.2010.02109.x. Epub 2010 Mar 17.


Aim: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Biomarkers / blood
  • Biomarkers / urine
  • Blotting, Western
  • Calcification, Physiologic
  • Calcitriol / blood
  • Female
  • Homeostasis
  • Hypophosphatemia, Familial / enzymology
  • Hypophosphatemia, Familial / genetics
  • Kidney Tubules / enzymology*
  • Male
  • Membrane Potentials
  • Mice
  • Mice, Knockout
  • Microvilli / enzymology
  • Parathyroid Hormone / blood
  • Patch-Clamp Techniques
  • Phosphates / metabolism*
  • Proto-Oncogene Proteins c-akt / deficiency
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Sodium / metabolism
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism*
  • Xenopus


  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Slc34a1 protein, mouse
  • Slc34a1 protein, rat
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Sodium
  • Akt2 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Calcitriol