INSULIN-LIKE GROWTH FACTOR-I STIMULATES PROTEIN SYNTHESIS IN SKELETAL MUSCLE IN THE NEONATE, BUT NOT LIVER AND GUT

Abstract

Skeletal muscle protein synthesis in the neonate in highly sensitive to nutrient intake, insulin, and amino acids. Insulin-like growth factor-I (IGF-I) is a regulator of both growth and differentiation in many cell types. To determine whether protein synthesis is sensitive to circulating physiological levels of IGF-I, fasted 7d and 26d old pigs were infused with no IGF-I (Oμg/kg/h), low IGF-I (20 μg/kg/h), high IGF-I (50 μg/kg/h), and high IGF-I plus replacement insulin (10 ng/kg0.66/min). Glucose and amino acids were clamped at fasting levels. Protein synthesis was determined with the flooding dose method. Plasma IGF-I levels during infusion in 7d were 10.6 ± 0.7, 19.6 ± 2.0, 26.7 ± 2.6, and 26.0 ± 3.1 ng/ml, and in 26d were 58.4 ± 13.4, 73.1 ± 11.5, 127.6 ± 17.6, and 103.8 ± 13.8 ng/ml, respectively. Plasma insulin levels in 7d pigs were 2.5 ± 0.6, 0.9 ± 0.3, 0.4 ± 0.2, and 3.3 ± 0.2 μU/ml, respectively, and in 26d pigs were 3.3 ± 0.8, 1.5 ± 0.3, 0.9 ± 0.5, and 2.8 ± 0.2 μU/ml, respectively. Circulating IGF-I significantly increased muscle protein synthesis in 7d (12.9 ± 0.3, 15.8 ± 0.4, 17.6 ± 0.8, and 18.8 ± 1.7%/d, respectively). Muscle protein synthesis response to IGF-I was decreased with age (4.7 ± 0.3, 5.9 ± 0.6, 5.6 ± 0.3, and 5.2 ± 0.2%/d, respectively). IGF-I infusion did not increase protein synthesis in the liver or gut in 7d or 26d old pigs. This data suggest that, in the neonate, muscle protein synthesis is highly sensitive and responsive to circulating IGF-I levels and that this response is blunted with development. This response to IGF-I, similar to our previously reported protein synthesis response to insulin, is specific for muscle and is not present in liver and gut of the neonate. Supported by NIH AR444 74 and USDA/ARS 6250–5100–031.