FETAL GLUCOSE AND AMINO ACID DEPRIVATION

营养剥夺引起的胎儿生长受限(FGR)导致胎儿 代谢适应包括胰岛素分泌和胰岛素减少 敏感度和蛋白质分解增加。这些适应可能 限制胎儿新陈代谢能力以成功应对 积极的营养疗法。在这个项目中，我们将使用我们建立的 胎儿葡萄糖和胰岛素缺乏(正常氨基酸血症)的FGR模型 和一种新的FGR模型，该模型将在 母亲低蛋白饮食加/减低氨基酸血症的具体目标#1 (血糖正常)，以测试这些FGR胎儿的反应如何 从新陈代谢到增加营养供应。我们将检验4个假设：1. 快速、高速率的葡萄糖输注到FGR胎儿体内将产生 过度的低氧血症、酸中毒和乳酸的产生；2.迅速、高 将选定的氨基酸注入FGR胎儿的速度将产生 他们的新陈代谢速度低于预期；3.进展缓慢 葡萄糖对FGR胎儿将使胰岛素分泌和胰岛素正常化 敏感度，可促进葡萄糖和氨基酸代谢；4.速度慢 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 酸代谢。实验将使用我们已建立的方法 底物和激素钳与Fick原理和示踪剂测量 量化胎儿营养底物的进入、利用和氧化速率。 这将是第一次研究确定氨基酸是如何供应给 胎儿调节胎儿胰岛素的分泌，第一批研究确定 如何将先前缺乏的营养重新引入FGR胎儿 影响胎儿新陈代谢，为规划未来临床提供必要数据 人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.