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)