title: PI3-kinase-dependent electrogenic intestinal transport of glucose and amino acids.
abstract: Intestinal glucose and amino acid transport is stimulated by the serum- and glucocorticoid-inducible kinase isoforms SGK1, SGK2, and SGK3 and protein kinase B which are, in turn, stimulated following activation of the phosphoinositol-3 kinase (PI3 kinase). The present study has been performed to explore whether pharmacological inhibition of the PI3 kinase affects electrogenic jejunal transport of glucose and amino acids. In Ussing chamber experiments, glucose (20 mM), phenylalanine (20 mM), glutamine (20 mM), cysteine (20 mM), and proline (20 mM) generated lumen negative currents (I (glc), I (phe), I (gln), I (cys), and I (pro)), respectively, which gradually declined following application of the PI3 kinase inhibitor Wortmannin (1 muM). Within 40 min, Wortmannin treatment significantly decreased I (glc) by 39 +/- 10% (n = 5), I (phe) by 70 +/- 7% (n = 4), I (gln) by 69 +/- 8% (n = 4), I (cys) by 67 +/- 8% (n = 6), and I (prol) by 79 +/- 12% (n = 3). A similar decline of I (glc) was observed following application of the PI3 kinase inhibitor LY294002 (50 microM). Exposure to the inhibitors did not significantly alter transepithelial potential difference and resistance in the absence of substrates for electrogenic transport. The observations suggest that the electrogenic transport of glucose and several amino acids requires the continued activity of PI3 kinase.
authors.affiliation: Department of Physiology I, University of Tübingen, Tübingen, Germany.
authors.forename: Rexhep
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
authors.forename: Marco
authors.initials: M
authors.lastname: Metzger
authors.forename: Thomas
authors.initials: T
authors.lastname: Skutella
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000596:Amino Acids / Q000493:pharmacokinetics*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003545:Cysteine / Q000493:pharmacokinetics; D015194:Diffusion Chambers, Culture; D004234:Diuretics, Osmotic / Q000493:pharmacokinetics; D017097:Electric Impedance; D005947:Glucose / Q000493:pharmacokinetics*; D005973:Glutamine / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008353:Mannitol / Q000493:pharmacokinetics; D051379:Mice; D010649:Phenylalanine / Q000493:pharmacokinetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011392:Proline / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077191:Wortmannin
chemical_list: D000596:Amino Acids; D000730:Androstadienes; D003545:Cysteine; D004234:Diuretics, Osmotic; D005947:Glucose; D005973:Glutamine; D008353:Mannitol; D010649:Phenylalanine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011392:Proline; D047428:Protein Kinase Inhibitors; D000077191:Wortmannin