GLUCOSE AND AMINO ACID METABOLISM IN PREGNANCY

拟议研究的目标是纵向量化 母体代谢对妊娠进展和胎儿生长发育的影响 胎儿。具体地说，怀孕和胎儿变化的影响 生长，例如在糖尿病中，依靠全身氨基酸和葡萄糖 新陈代谢将使用稳定同位素示踪法进行量化。数据 我们之前对人类怀孕的研究表明，虽然变化 在能量传递底物中，例如葡萄糖和脂肪酸，在 怀孕与母亲的能量需求是平行的， 发育中的胚胎，蛋白质/氮代谢中的适应性反应 出现在对胎儿需求的预期中。此外，初步数据 提示：(A)肝/内脏组织可能是一个重要的器官系统 参与与妊娠有关的适应，以及(B)氨基酸 转氨酶作用可能是氮素保护和 吸积作用。拟议中的研究旨在检验这两个假说。 将同时使用多种同位素示踪剂来量化 内脏提取和代谢必需氨基酸。全身 尿素和胎儿的主要氮源谷氨酰胺的动力学 它的氮源将被量化。因为胎儿巨大儿已经 仍然是妊娠期糖尿病的长期问题，尽管 严谨的干预策略，这种异常胎儿的临床模型 将根据糖异生和氨基酸的变化来评估生长。 新陈代谢。一种新开发的利用身体标记的新方法 已经用于正常妊娠的水将用于 量化妊娠期糖尿病患者的糖异生。这些研究将 人体内关键营养素和底物的定量动力学 (母亲和胎儿)，这会影响胎儿的生长。预计 这些数据将使制定干预战略成为可能 改善异常胎儿发育。

The objectives of the proposed studies are to quantify longitudinally maternal metabolic responses to progressions of pregnancy and growth of the fetus. Specifically, the impact of pregnancy and alterations in fetal growth, e.g. in diabetes, upon whole body amino acid and glucose metabolism will be quantified using stable isotope tracer method. Data from our previous studies in human pregnancy have shown that while changes in energy delivering substrates, e.g. glucose and fatty acids, during pregnancy occur parallel with the energy requirements of the mother and growing conceptus, adaptive responses in protein/nitrogen metabolism appear in anticipation of the fetal needs. In addition, preliminary data suggest that (a) liver/splanchnic tissue may be an important organ system involved in the pregnancy related adaptation, and (b) amino acid transamination may be an important component of nitrogen conservation and accretion. The proposed studies are aimed at testing these two hypotheses. Multiple isotope tracers will be used simultaneously to quantify splanchnic extraction and metabolism of essential amino acids. Whole body kinetics of glutamine, a major nitrogen source for urea and for the fetus and its nitrogen source will be quantified. Since fetal macrosomia has continued to be a persistent problem in gestational diabetes despite rigorous intervention strategies, this clinical model of abnormal fetal growth will be evaluated for the changes in gluconeogenesis and amino acid metabolism. A recently developed novel method employing labeling of body water which has already been applied to normal pregnancy will be used to quantify gluconeogenesis in gestational diabetes. These studies will quantify kinetics of key nutrients and substrates in the whole body (mother and fetus) which can impact fetal growth. It is anticipated that these data will permit the development of intervention strategies for amelioration of aberrant fetal growth.