The accelerated rate of protein accretion in the immature muscle is driven by its ability to attain high rates of protein synthesis when nutrients are in plentiful supply. This response is facilitated by a heightened sensitivity of protein synthesis to insulin and nutrients. Recent studies have demonstrated that local insulin-like growth factors (IGFs) acting in an autocrine/paracrine manner are principally responsible for regulating postnatal somatic growth. Therefore, my hypothesis is that the high local abundance of IGF-I in the immature muscle enhances the response of muscle protein synthesis to feeding primarily by enhancing the sensitivity of muscle to insulin. To test my hypothesis I propose the following Specific Aims: 1) to determine if the stimulation of muscle protein synthesis by feeding is greater when local tissue IGF-I levels are high; 2) to determine if the feeding-induced stimulation of muscle protein synthesis is more sensitive to insulin compared to nutrients when muscle IGF-I concentrations are elevated; 3) to determine if the heightened sensitivity of the immature muscle to insulin by local IGF-I is due to inhibition of protein tyrosine phosphatase (PTP)1B activity; 4) to determine if low PTP1B activity associated with high muscle IGF-I prolongs the activation of the insulin receptor.
