Akt2/PKBβ-sensitive regulation of renal phosphate transport

Akt2/PKBβ-sensitive regulation of renal phosphate transport

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. The renal phosphate transporter NaPi-IIa was expressed in...

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Bibliographic Details
Published in:Acta Physiologica Vol. 200; no. 1; pp. 75 - 85
Main Authors: 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
Format: Journal Article
Language:English
Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-09-2010
Blackwell Publishing Ltd
Wiley-Blackwell
Subjects:
Biological and medical sciences
bone density
calcium
Fundamental and applied biological sciences. Psychology
insulin
kidney
kidneys
metabolism
PTH
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Xenopus
Phosphates
Pancreatic hormone
Calcium
PTH
Biological transport
Peptide hormone
bone density
Metabolism
Inorganic element
Density
Insulin
Kidney
Osteoarticular system
Vertebrata
Mammalia
Urinary system
Parathyroid hormone
Bone
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Summary: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. 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/PKBβ knockout mice (akt2⁻/⁻) and corresponding wild-type mice (akt2⁺/⁺). Transporter protein abundance was determined using Western blotting and phosphate transport by ³²P uptake into brush border membrane vesicles. The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [μmol 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 D₃ concentration (by 46%). Moreover, fractional renal Ca²⁺ excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2⁻/⁻ mice. Akt2/PKBβ 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.
Bibliography:http://dx.doi.org/10.1111/j.1748-1716.2010.02109.x
ArticleID:APHA2109
istex:097C431D018226D84AD21681DEDF385BC0E9DEB0
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The two authors contributed equally and thus share first authorship.
ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:1748-1708
1748-1716
DOI:10.1111/j.1748-1716.2010.02109.x