CARBOHYDRATE HOMEOSTASIS IN THE NEONATE

新生儿的碳水化合物稳态

• 批准号: 2200350
• 负责人: RICHARD M COWETT
• 金额: $ 18.87万
• 依托单位: WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2200350
• 关键词: blood glucose; carbohydrate balance; developmental nutrition; galanin; gas chromatography mass spectrometry; glucose metabolism; glucose transport; homeostasis; hormone regulation /control mechanism; human subject; hyperinsulinism; hypoglycemia; insulin; neuropeptides; newborn animals; newborn human (0-6 weeks); pancreatic islet function; premature infant human; radiotracer; sheep; stable isotope

These studies compliment and extend investigations performed in this laboratory to evaluate the hormonal mechanisms controlling development of neonatal glucose homeostasis. Developmentally, the neonate is in a transitional state of glucose homeostasis. While the fetus is completely dependent on his/her mother for glucose delivery, the adult has control of glucose homeostasis since glucose concentration is regulated precisely. In contrast, regulation of glucose may be a major problem even in the term neonate. The neonate must maintain a balance between glucose lack and excess. The dependence of the conceptus on the maternal organism for continuous substrate delivery contrasts with intermittent oral intake by the neonate. Homeostasis should result from an improving balance between developing hormonal systems (insulin and contra-insulin effects, sympathomimetics and neural). These interrelated studies, continuing nineteen years of neonatal carbohydrate kinetic research, will utilize established techniques of our laboratory, available in only a few neonatal laboratories nationally and internationally. We will study kinetics in the term lamb using radioactive isotopes and in the preterm and term human neonate using stable isotopes to answer hypotheses about hormonal control. The first series of studies evaluate the effects of various counter regulatory hormones individually on the suppressed splanchnic (primary hepatic) response to insulin. These studies will use a hypoglycemic hyperinsulinemia model in the neonatal lamb. A second series in the neonatal lamb combines the euglycemic hyperinsulinemic clamp technique with tracer kinetics to evaluate the differential sensitivity of insulin for glucose production versus glucose utilization. Also, we will use sequential doses of galanin, a post ganglionic neurotransmitter, which selectively inhibits insulin secretion to evaluate differential sensitivity to decrements in insulin availability. A third series, studying the human neonate, evaluates regulation of glucose production in response to glucose delivery. These coordinated studies are designed to definitively evaluate the ontogeny of hormonal regulation of neonatal glucose homeostasis. They are critical to our understanding of the physiologic basis of nutritional support neonates require.

这些研究称赞并扩展了对此进行的调查 实验室评估控制开发的激素机制 新生儿葡萄糖稳态。从发展上讲，新生儿在 葡萄糖稳态的过渡状态。而胎儿完全 取决于他/她的母亲进行葡萄糖的递送，成年人控制 葡萄糖稳态由于葡萄糖浓度受到精确调节。 相比之下，即使在此期间，葡萄糖的调节也可能是一个主要问题 新生儿。新生儿必须保持葡萄糖不足和 过量的。概念对孕产妇生物的依赖性 连续的底物递送与间歇性口服摄入的对比 新生儿。 体内平衡应是由于提高的平衡而产生的 发展激素系统（胰岛素和互胰岛素作用， 交感神经和神经）。这些相互关联的研究，继续 新生儿碳水化合物动力学研究十九年将利用 我们实验室的既定技术，仅提供几个新生儿 实验室在国内和国际上。我们将研究动力学 使用放射性同位素以及在早产和人类中的术语羔羊 使用稳定的同位素回答有关激素对照的假设。 第一系列研究评估了各种计数器的影响 在被抑制的斑点上单独的监管激素（主要 肝）对胰岛素的反应。 这些研究将使用降血糖 新生儿羔羊中的高胰岛素血症模型。第二个系列 新生儿羔羊结合了葡萄糖高胰岛素夹技术 使用示踪剂动力学来评估胰岛素的差异灵敏度 用于葡萄糖生产与葡萄糖利用率。另外，我们将使用 顺序剂量的galanin，一种神经节神经递质后的galanin，该剂量 有选择地抑制胰岛素分泌以评估差异 对胰岛素可用性减少的敏感性。第三系列， 研究人类新生儿，评估葡萄糖产生的调节 对葡萄糖递送的反应。这些协调的研究旨在 明确评估新生儿激素调节的个体发育 葡萄糖稳态。他们对我们对 营养支持新生儿的生理基础。