ROLE OF INSULIN AND IGF-I IN ACTIVATION OF MUSCLE PROTEIN-SYNTHESIS AFTER ORAL-FEEDING

The aim was to evaluate the role of insulin and insulin-like growth fa ctor I(IGF-I) in activation of muscle protein synthesis after oral fee ding. Synthesis rate of globular and myofibrillar proteins in muscle t issue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal(C57 B1) an d diabetic mice (type I and type II) were subjected to an overnight fa st (18 h) with subsequent refeeding procedures for 3 h with either ora l chow intake or provision of insulin, IGF-I, glucose, and amino acids . Antiinsulin and anti-IGF-I were provided intraperitoneally before or al refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/refeeding, was proportional and similar t o changes in skeletal muscle IGF-I mRNA expression. Diabetic mice resp onded quantitatively similarly to starvation/refeeding in muscle prote in synthesis compared with normal mice (C57 B1). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or TGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our resul ts support the suggestion that insulin and IGF-I either induce or faci litate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feedin g.