Effects of insulin-like growth factor I on phosphate transport in cultured proximal tubule cells.
In vivo, proximal tubule cells are exposed to insulin-like growth factor I (IGF-I) that is present in serum or in proximal tubule fluid. For example, in the nephrotic syndrome, proximal tubule fluid contains IGF-I at biologically meaningful concentrations in association with IGF-binding protein-2 (IGFBP-2). IGF-I has also been shown to decrease the urinary excretion of phosphate (Pi) in normal subjects. We hypothesized that IGF-I can raise tubule cell Pi absorption directly through an apical as well as a basolateral tubule receptor mechanism, specifically, through IGF-I (type I) receptors as compared to IGF-II (type II) or insulin receptors. Studies were performed in cultured proximal tubule cells that express high-affinity IGF-I receptors. Stimulation of cells selectively at the apical or basolateral membrane with IGF-I (10(-9) to 10(-7) mol/L) increases Pi absorption by up to 80%, but a significant counterdirectional Pi flux in the apical-to-basolateral direction does not occur. The effect of IGF-I on Pi transport appears to be specific inasmuch as the transport of alanine is not affected by the peptide. IGFBP-2 does not inhibit this effect of IGF-I, but the IGF-I-induced increase in Pi transport is inhibited by a neutralizing anti-IGF-I receptor monoclonal antibody. Exposure of the cells to IGF-II (10(-7) mol/L) but not to insulin selectively at the apical membrane tends to increase Pi transport, and this IGF-II effect is also blocked by the anti-IGF-I receptor antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirschberg
R
R
Division of Nephrology & Hypertension, Harbor-UCLA Medical Center, Torrance 90509, USA.
Ding
H
H
Wanner
C
C
D000042:Absorption; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010710:Phosphates / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D018971:Insulin-Like Growth Factor Binding Protein 2; D010710:Phosphates; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1