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Akt2/PKBbeta-sensitive regulation of renal phosphate transport.

Authors: Kempe, DS  Ackermann, TF  Boini, KM  Klaus, F  Umbach, AT  Dermaku-Sopjani, M  Judenhofer, MS  Pichler, BJ  Capuano, P  Stange, G  Wagner, CA  Birnbaum, MJ  Pearce, D  Foller, M  Lang, F 
Citation: Kempe DS, etal., Acta Physiol (Oxf). 2010 Sep;200(1):75-85. doi: 10.1111/j.1748-1716.2010.02109.x. Epub 2010 Mar 17.
Pubmed: (View Article at PubMed) PMID:20236253
DOI: Full-text: DOI:10.1111/j.1748-1716.2010.02109.x

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.

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CRRD Object Information
CRRD ID: 7243105
Created: 2013-05-02
Species: All species
Last Modified: 2013-05-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.