Akt2/PKBβ-sensitive regulation of renal phosphate transport

• 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
• DOI: 10.1111/j.1748-1716.2010.02109.x
• EISSN: 1748-1716
• ISSN: 1748-1708

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.