HORMONAL REGULATION OF NEONATAL MUSCLE PROTEIN SYNTHESIS

描述（改编自申请人摘要）：净蛋白质增加 对新生儿的生长至关重要。 长期目标是 确定使营养素、激素和生长 调节骨骼肌高增长率的因素 出生后早期的蛋白质。 这种升高的肌肉蛋白质 增长与肌肉蛋白质的增强刺激有关 通过摄入营养物合成。 肌肉蛋白质增生，核糖体 浓度，营养素刺激的肌肉蛋白质合成下降 在哺乳期内平行进行。 研究人员假设， 出生后肌肉蛋白质合成的反应下降， 营养摄入是由于肌肉蛋白质的敏感性下降 合成胰岛素，以及胰岛素样生长因子-I的下降 肌肉中的胰岛素样生长因子-I（IGF-I）丰度是导致胰岛素水平下降的原因。 灵敏度 目的1是确定出生后早期的变化， 骨骼肌蛋白质合成对急性增加的敏感性 胰岛素 为了实现这一点，在体内胰岛素剂量反应的肌肉 蛋白质合成和核糖体RNA（rRNA）丰度将被确定 在7日龄和26日龄乳猪中， 同时使用一种新的氨基酸钳，研究人员已经 开发 目的2是确定氨基酸供应的直接作用 对肌肉蛋白质合成的影响， 对胰岛素刺激肌肉蛋白质合成的影响。 实现 肌肉蛋白质合成和rRNA丰度的反应， 单独输注氨基酸期间血浆氨基酸水平升高， 在高胰岛素正常血糖钳夹期间，将在7-和 26岁的猪 目的3是确定出生后早期的变化， 肌肉蛋白质合成对IGF-I急性增加的反应。 为了实现这一点，肌肉蛋白质合成和rRNA的反应 急性输注IGF-I的丰度，而基础空腹血浆 胰岛素、葡萄糖和氨基酸是否得到维持，将在 7-26日龄的猪 目的4是确定是否延长 IGF-I的升高增强了肌肉蛋白的胰岛素敏感性 合成. 为了实现这一点，长期输注IGF-I的效果 对胰岛素敏感性的影响 丰度将在高胰岛素正常血糖期间测定。 在26日龄猪中进行的euminoacidemic夹。 这项工作的重要性 是确定调节肌肉蛋白质机制 新生儿的增生将揭示新的策略，以优化使用 生长期新生儿肌肉蛋白沉积的氨基酸 失败，它将建立使用的生理基础， IGF-I治疗低出生体重和生长迟缓 婴儿。

DESCRIPTION (Adapted from applicant's abstract): Net protein accretion is essential for the growth of neonates. The long-term objective is to determine the mechanisms which enable nutrients, hormones, and growth factors to regulate the high rate of accretion of skeletal muscle proteins during early postnatal life. This elevated muscle protein accretion is associated with an enhanced stimulation of muscle protein synthesis by nutrient intake. Muscle protein accretion, ribosomal concentration, and nutrient-stimulated muscle protein synthesis decline in parallel over the suckling period. The investigators hypothesize that the postnatal decline in the response of muscle protein synthesis to nutrient intake is due to a decline in the sensitivity of muscle protein synthesis to insulin, and that a decline in insulin-like growth factor-I (IGF-I) abundance in muscle is responsible for this decline in insulin sensitivity. AIM 1 is to determine the early postnatal changes in the sensitivity of skeletal muscle protein synthesis to acute increases in insulin. To achieve this, the in vivo insulin does-response of muscle protein synthesis and ribosomal RNA (rRNA) abundance will be determined in 7- and 26-day-old suckling pigs during hyperinsulinemic euglycemic clamps while using a novel amino acid clamp which the investigators have developed. AIM 2 is to determine the direct effect of amino acid supply on muscle protein synthesis during the early postnatal period, and its influence on insulin-stimulated muscle protein synthesis. To achieve this, the response of muscle protein synthesis and rRNA abundance to elevated plasma amino acid levels during amino acid infusion alone and during hyperinsulinemic euglycemic clamps will be determined in 7- and 26-day-old pigs. AIM 3 is to determine the early postnatal changes in the response of muscle protein synthesis to acute increases in IGF-I. To achieve this, the response of muscle protein synthesis and rRNA abundance to acute infusions of IGF-I, while basal fasting plasma insulin, glucose, and amino acids are maintained, will be determined in 7- and 26-day-old pigs. AIM 4 is to determine whether prolonged elevations in IGF-I enhance the insulin sensitivity of muscle protein synthesis. To achieve this, the effect of a chronic infusion of IGF-I on the insulin sensitivity of muscle protein synthesis and rRNA abundance will be determined during hyperinsulinemic euglycemic euaminoacidemic clamps in 26-day-old pigs. The importance of this work is that identification of the mechanisms that regulate muscle protein accretion in the neonate will reveal new strategies to optimize the use of amino acids for muscle protein deposition in neonates with growth failure, and it will establish the physiological basis for the use of IGF-I in the treatment of both low-birth-weight and growth-retarded infants.