Aims: Insulin stimulates Na absorption in the distal nephron and this may contribute to the development of salt-dependent hypertension in 2 diabetes patients. Whilst this Na retaining action is usually attributed to signalling via phosphatidylinositol-3-kinase (PI3K) / serum- glucocortiocoid-inducible kinase 1 (SGK1), there is evidence that protein kinase B (PKB), another PI3K target, may also be important (Lee et al., 2007). The present study therefore aimed to assess the relative importance of these kinases. Methods. Confluent mpkCCD cells were mounted in Ussing chambers and the effects of Akti-1/2 and GSK650394A on insulin-evoked Na transport studied electrometrically. Effects on cellular PKB and SGK1 activities were explored by monitoring (Western analysis) the phosphorylation of endogenous proteins. Results. Akti-1/2 (1 – 10 M) caused concentration dependent inhibition of insulin-induced Na absorption and blocked the insulin-evoked phosphorylation of a PKB substrate (PRAS40- Ser²⁴⁶). However, Akti-1/2 also suppressed the phosphorylation of residues within the protein encoded by N-myc-downstream regulated gene 1 (NDRG1- Thr^346/356/366) that are substrates for SGK1 and not PKB (Murray et al., 2005). At 10 mM, GSK650394A abolished insulin-evoked Na absorption (96.8 ± 4.3 % inhibition, P < 0.05) and suppressed PRAS40-Ser²⁴⁶ and NDRG1-Thr^346/356/366 phosphorylation. However, lower concentrations of GSK650394A significantly inhibited insulin- evoked Na+ absorption (1 mM, 44.6 ± 7.3 %, P < 0.0x, P < 0.02; 3 mM, 55.5 ± 2.7 %, P < 0.001) and blocked NDRG1- Thr^346/356/366 phosphorylation selectively. Conclusion. Akti-1/2 does not inhibit PKB selectively in mpkCCD cells but studies using GSK65094A indicate that insulin evoked Na transport is mediated via SGK1 rather than PKB in these cells. Lee, I.-H. et al. (2007). J. Biol. Chem. 282, 29866-29873 Murray, J.T. et al. (2005). Biochem. J. 385, 1- 12.