The activation of insulin signaling components leading to mRNA translation in skeletal muscle of neonatal pigs is developmentally regulated

Abstract

Insulin and amino acids can act independently to stimulate skeletal muscle protein synthesis in neonatal pigs. The purpose of this study was to elucidate the developmental regulation of the activation of signaling components leading to protein synthesis in skeletal muscle that is induced by insulin. Hyperinsulinemic-euglycemic-euaminoacidemic clamps were performed in fasted 6-d (n = 4) and 26-d-old pigs (n = 6) to raise plasma insulin levels from 5 (fasting level) to 30 (fed level) μU/ml. Insulin increased the fractional rate of protein synthesis in muscle (P<0.05) and this response decreased with development (P<0.05). Insulin increased the phosphorylation of PKB, mTOR, S6K1, and 4E-BP1 and the response to insulin was higher in 6-d compared to 26-d-old pigs (P<0.05). In 6-d-old pigs, there was a tendency for insulin to reduce the binding of raptor to mTOR (P=0.08). Insulin decreased the binding of 4E-BP1 to eIF4E (P<0.05) and increased eIF4E binding to eIF4G (P<0.05). These effects were greater in 6-d than in 26-d-old pigs (P<0.05). Furthermore, neither insulin nor age affected the phosphorylation of eEF2. Our results suggest that the activation of many of the insulin signaling components leading to mRNA translation in muscle is developmentally regulated and parallels the developmental decline in protein synthesis in skeletal muscle of neonatal pigs. NIH AR44474, USDA 58-6250-6-001