Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-35763
Kempe, D S; Ackermann, T F; Boini, K M; Klaus, F; Umbach, A T; Dërmaku-Sopjani, M; Judenhofer, M S; Pichler, B J; Capuano, P; Stange, G; Wagner, C A; Birnbaum, M J; Pearce, D; Föller, M; Lang, F (2010). Akt2/PKBbeta-sensitive regulation of renal phosphate transport. Acta Physiologica, 200(1):75-85.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||05 Nov 2010 08:17|
|Last Modified:||23 Nov 2012 13:05|
|Additional Information:||© The Authors 2010. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Acta Physiol 2010, 200, 75–85. http://dx.doi.org/10.1111/j.1748-1716.2010.02109.x|
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