Insulin-like growth factor I stimulates Na-dependent Pi transport in cultured kidney cells

Abstract

The effect of recombinant insulin-like growth factor I (IGF-I/somatomedin C) on the transport of inorganic phosphate (Pi) was studied in cultured kidney epithelia. In opossum kidney (OK) epithelia, IGF-I (5 x 10(-10) to 10(-7) M) induced a dose-related stimulation of the Na-dependent Pi transport (NaPiT). A maximal response was observed at 10(-7) M (IGF-I 1.64 +/- 0.12; vehicle 0.90 +/- 0.02 nmol.mg protein-1. 4 min-1, P less than 0.001). Kinetic analysis of the stimulatory effect of IGF-I on NaPiT indicated an increase in Vmax and no change in Km. Insulin also stimulated NaPiT in OK epithelia but only at concentrations 20-40 times higher than IGF-I. The effect of IGF-I on Pi transport was detectable in less than 30 min with a maximal response occurring after 4-5 h. It was selective for NaPiT, since the Na-dependent alanine transport was not affected by IGF-I. Inhibition of protein synthesis by either cycloheximide or cordycepin markedly attenuated the stimulatory effect of IGF-I on NaPiT. The cellular adenosine 3',5'-cyclic monophosphate content was not modified by the growth factor. In conclusion, these data indicate that IGF-I increases NaPiT selectively through a mechanism that involves de novo protein synthesis. These observations suggest that growth and growth hormone-related stimulation of renal Pi transport could be mediated by IGF-I.