Insulin-like growth factor I stimulates active Na(+)-K+ transport in rat soleus muscle

The functional homology between insulin and insulin-like growth factor I (IGF-I) comprises effects on growth and glucose metabolism. Because insulin stimulates the Na(+)-K+ pump, IGF-I might exert a similar effect. We show here that IGF-I increases 42K and 86Rb uptake and the efflux of 22Na in isolated rat soleus muscle. This leads to a significant decrease (21-55%, P < 0.001) in intracellular Na+ and a small increase in intracellular K+. In extensor digitorum longus (EDL) muscle, similar effects were observed. The stimulation of K+ uptake and the reduction in intracellular Na+ in the soleus were blocked by ouabain, indicating that they reflect an acute stimulation of active Na(+)-K+ transport. This conclusion was further supported by the observation that the [3H]ouabain binding rate was significantly increased by IGF-I. IGF-I increased ouabain-suppressible 42K or 86Rb uptake by 56 and 54%, respectively. The effects of IGF-I and epinephrine on ouabain-suppressible 86Rb influx in rat soleus were additive, whereas the effects of insulin and IGF-I were similar and nonadditive. The effects of IGF-I were seen down to a concentration of 10(-8) M, which is unlikely to stimulate the insulin receptor, and it is therefore plausible that IGF-I exerts its effect on Na(+)-K+ transport through its own receptor. IGF-I may play a role in the maintenance of muscle Na+ and K+ contents also in vivo, especially in patients treated with IGF-I.