GLUCOSE AND AMINO ACID METABOLISM IN PREGNANCY

怀孕期间的葡萄糖和氨基酸代谢

• 批准号: 6444000
• 负责人: SATISH C KALHAN
• 金额: $ 15.33万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6444000
• 关键词: aminoacid metabolism; bioenergetics; calorimetry; clinical chemistry; clinical research; essential aminoacid; gestational age; gestational diabetes mellitus; glucose metabolism; glutamine; glycogenolysis; high performance liquid chromatography; human pregnant subject; human subject; longitudinal human study; nitrogen metabolism; perinatal; plethysmography; pregnancy; prenatal growth disorder; protein metabolism; stable isotope; statistics /biometry; striated muscles; aminoacid metabolism; bioenergetics; calorimetry; clinical chemistry; clinical research; essential aminoacid; gestational age; gestational diabetes mellitus; glucose metabolism; glutamine; glycogenolysis; high performance liquid chromatography; human pregnant subject; human subject; longitudinal human study; nitrogen metabolism; perinatal; plethysmography; pregnancy; prenatal growth disorder; protein metabolism; stable isotope; statistics /biometry; striated muscles

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.

拟议研究的目标是纵向量化 孕产妇对怀孕进展和生长的代谢反应 胎儿。具体而言，怀孕和胎儿改变的影响 增长，例如在糖尿病中，全身氨基酸和葡萄糖 代谢将使用稳定的同位素示踪剂方法进行量化。数据 从我们先前在人类怀孕的研究中，尽管发生了变化 在能量传递基材上，例如葡萄糖和脂肪酸，期间 怀孕与母亲的能量要求平行， 日益增长的概念，蛋白质/氮代谢中的自适应反应 出现时要预期胎儿需求。此外，初步数据 建议（a）肝脏/斑点组织可能是重要的器官系统 参与妊娠相关的适应性，（b）氨基酸 跨化可能是氮保养和 积聚。拟议的研究旨在检验这两个假设。 多个同位素示踪剂将同时使用来量化 必需氨基酸的诊断提取和代谢。全身 谷氨酰胺的动力学，尿素和胎儿的主要氮来源 并将量化其氮源。由于胎儿大粒病具有 尽管 严格的干预策略，这种异常胎儿的临床模型 将评估糖异生和氨基酸的变化的生长 代谢。最近开发的新方法采用身体标签 已经应用于正常怀孕的水将用于 量化妊娠糖尿病中的糖异生。这些研究会 量化全身关键营养素和底物的动力学 （母亲和胎儿）会影响胎儿生长。预计 这些数据将允许制定干预策略 改善异常胎儿生长。