Modulation of Pi transport in skeletal muscle by insulin and IGF-1

In vivo, skeletal muscle Pi uptake influences both muscle cellular [Pi] and plasma [Pi], and may mediate the hypophosphataemic effects of insulin and insulin-like growth factor 1 (IGF-1). These effects were investigated in the cultured mouse myoblast cell line G8 and the isolated incubated rat soleus. The low Km for Pi in G8 cells is consistent with in vivo evidence that muscle cell [Pi] is partially protected against changes in plasma [Pi]. Insulin and IGF-1 stimulated Na-dependent Pi influx: in G8 cells both increased Vmax, with no change in Km, but while the insulin response occurred within 15 min and rapidly reversed upon insulin withdrawal, the response to IGF-1 occurred only after 60 min and persisted at least 60 min following IGF-1 withdrawal. Furthermore, only the IGF-1 response was inhibited by cycloheximide. We suggest that IGF-1 operates through de novo protein synthesis, while insulin stimulates transporter recruitment to the cell surface.