FETAL GLUCOSE AND AMINO ACID DEPRIVATION

营养缺乏导致胎儿生长受限（FGR）， 代谢适应，包括胰岛素分泌减少和胰岛素 敏感性和增加的蛋白质分解。 这些适应可能 限制胎儿的代谢能力，以成功地应对 积极的营养治疗 在这个项目中，我们将使用我们的既定 胎儿葡萄糖和胰岛素缺乏的FGR模型（伴正常氨基酸血症） 从母体低血糖，和一个新的FGR模型将开发下 产妇低蛋白饮食加/减低氨基酸血症的具体目标#1 (with normoprotein），以测试这些FGR胎儿的反应如何 增加营养供应。 我们将测试4个假设：1。 快速、高速率的葡萄糖输注到FGR胎儿中将产生 过度低氧血症、酸中毒和乳酸产生; 2.快速，高 将选定的氨基酸输注到FGR胎儿中的速率将产生 低于预期的新陈代谢率; 3.缓慢引进 葡萄糖对FGR胎儿将正常化胰岛素分泌和胰岛素 敏感性，允许增加葡萄糖和氨基酸代谢; 4.慢 将氨基酸引入FGR胎儿将使胰岛素正常化 分泌和胰岛素敏感性，允许增加葡萄糖和氨基 酸代谢 实验将使用我们建立的方法， 基质和激素钳和菲克原理和示踪测量， 定量胎儿营养底物进入、利用和氧化速率。 这些将是第一个研究，以确定如何氨基酸供应， 胎儿调节胎儿胰岛素分泌，第一个研究，以确定 如何将先前缺乏的营养重新引入FGR胎儿 影响胎儿代谢，为计划未来的临床 人类FGR的营养治疗试验。

Fetal growth restriction (FGR) from nutrient deprivation results in fetal metabolic adaptations including decreased insulin secretion and insulin sensitivity, and increased protein breakdown. These adaptations might limit fetal metabolic capacity to respond successfully to attempts at aggressive nutrient therapy. In this project, we will use our established FGR model of fetal glucose and insulin deficiency (with normoaminacidemia) from maternal hypoglycemia, and a new FGR model to be developed under Specific Aim #1 of maternal low-protein diet plus/minus hypoaminoacidemia (with normoglycemia), to test how well these FGR fetuses respond metabolically to increased nutrient supply. We will test 4 hypotheses: 1. rapid, high rates of glucose infusion into the FGR fetus will produce excessive hypoxemia, acidosis, and lactate production; 2. rapid, high rates of infusion of selected amino acids into the FGR fetus will produce less than expected rates of their metabolism; 3. slow introduction of glucose to the FGR fetus will normalize insulin secretion and insulin sensitivity, allowing increased glucose and amino acid metabolism; 4. slow introduction of amino acids to the FGR fetus will normalize insulin secretion and insulin sensitivity, allowing increased glucose and amino acid metabolism. Experiments will use our established methods of substrate and hormone clamps and Fick principle and tracer measurements to quantify fetal nutrient substrate entry, utilization, and oxidation rates. These will be the first studies to determine how amino acid supply to the fetus regulates fetal insulin secretion, and the first studies to define how reintroduction of previously deficient nutrients to the FGR fetus affects fetal metabolism, providing essential data to plan future clinical trials of nutrient therapy of human FGR.