ASSESSMENT OF SUBSTRATE KINETIC ANALYSIS USING TRACERS

量化底物中急性、非稳定状态变化的能力 在体内代谢调节的研究中，动力学是必不可少的。 为此目的设计了同位素示踪技术。最多的 常见的方法是单池模型，已知基于不正确的 假设当应用于葡萄糖动力学时，这已经被证明 在几项研究中发现，在快速变化的情况下是不可靠的。两个- 泳池模式也被描述过，但并未被广泛接受。我们的 假设是目前计算非稳定等离子体的方法， 葡萄糖动力学可以通过两个创新来改善：(1)。基本模型 葡萄糖浓度和富集检测技术的研究进展 它们所在的两个主要隔室的胰岛素浓度 分布：血浆和间质液体。间质流体 测量将通过从长期放置的插管中取样获得 在绵羊的胸腔导管里。(2)。数据分析将涉及SO- 称为“直接”方法，它利用支配差异 方程式，从而允许规定的统计估计精度。 为了评估这种方法的适用性，将进行以下实验 在清醒的绵羊和正常的人类志愿者身上进行试验。实验 将在恒定或变化的胰岛素和 葡萄糖浓度。在后一种情况下，这些方程将解释 速率参数值与 普遍存在的胰岛素和葡萄糖浓度。 鉴于这种新的建模方法的测试将集中在 葡萄糖，它不是限制性的，我们预计在这些之后 验证实验该方法将在研究中得到广泛应用 各种各样的化合物。

The ability to quantify acute, non-steady state changes in substrate dynamics is imperative in the study of in vivo regulation of metabolism. Isotopic tracer techniques have been devised for this purpose. The most common approach is a single-pool model, known to be based on incorrect assumptions when applied to glucose kinetics, which has been demonstrated in several studies to be unreliable in rapidly changing situations. Two- pool models have also been described, but not widely accepted. Our hypothesis is that current methods for the calculation of non-steady plasm, a glucose kinetics can be improved by two innovations: (1). Basing model development on the measurement of glucose concentration and enrichment and insulin concentration in the two major compartments in which they are distributed: plasma and interstitial fluid. Interstitial fluid measurements will be obtained by sampling from a cannula chronically placed in the thoracic duct of sheep. (2). Data analysis will involve the so- called "direct" approach, which makes use of the governing differential equations, thereby allowing prescribed precision of statistical estimation. In order to assess the applicability of this approach, experiments will be performed in conscious sheep and in normal human volunteers. Experiments will be performed in the setting of either constant or varying insulin and glucose concentrations. In the later cases, the equations will account for the relationship between the values for the rate parameters and the prevailing insulin and glucose concentrations. Whereas the tests of this new approach to modeling will be focused on glucose, it is not restrictive and we anticipate that subsequent to these validation experiments the approach will become widely applied to the study of a variety of compounds.