CARBOHYDRATE AND LIPID METABOLIC PATHWAYS

长期目标是开发和应用量化的方法 碳水化合物和脂肪代谢的途径。其具体目的是 开发一种安全的估计糖异生速率的方法， 可靠、明确、易于执行和广泛适用，并加以应用 关于碳水化合物新陈代谢的假设的测试 生理和病理情况，重点是糖尿病患者 州政府。D2O的剂量是安全的，耐受性很好。在禁食中 由6个当量的甲醛形成的六亚甲基四胺是 用于测量与碳2、5和5结合的氚的丰度 6%的葡萄糖。含有与碳6结合的重氢的甲醛是 在血糖的高周期酸氧化作用下形成。甲醛 木糖氧化生成与碳5结合的含氢元素 由葡萄糖形成。在碳2中含有重氢的甲醛是 由葡萄糖生成的核糖醇-5-P氧化而成。在美联储 在美国，D2O是与对乙酰氨基酚一起服用的。结合在碳2上的重氢 和5%的葡萄糖是由排泄物的葡萄糖糖醛酸部分形成的 葡萄糖醛酸苷测定。葡萄糖输出量的比例由 禁食状态下的糖异生与糖原生成分数 通过在饲料状态下的糖异生作用，也与在 碳含量是人体水中碳含量的5倍。碳5与碳6的比率是 甘油对糖异生作用的测定及其影响程度 丙酮酸的氢与水中的氢的平衡。 禁食状态下的糖异生的绝对速率估计如下 用测得的葡萄糖产量乘以糖异生作用所得的分数 使用氚葡萄糖或(6，6-D2)葡萄糖。在美联储状态下，数量 使用MRI测量形成的糖原的数量，以估计肝脏体积和 13CNMR糖原浓度。在禁食状态下，使用磁共振成像和核磁共振 将糖异生速率的估计值与糖原分解速率联系起来。 将在正常受试者、肥胖受试者和 在NIDDM和MODY患者中。 这些发现应该与肝脏在生产过程中的作用有关 糖尿病患者的高血糖。这反过来又关系到 治疗药物与胰岛素全身给药的充分性 使新陈代谢恢复正常，而不仅仅是血糖浓度。这个 首次允许安全方便地提供D2O 在葡萄糖中获得足够的标记以测量 其形成和转化为糖原的途径。因为小的 必须给出的剂量的氢化水和少量的 分析所需的葡萄糖，该方法应适用于 儿科以及S成人的临床研究。

The long term objective is to develop and apply methods for quantitating pathways of carbohydrate and lipid metabolism. The specific aim is to develop a method for estimating rates of gluconeogenesis which is safe, reliable, definitive, easily performed, and broadly applicable, an apply it to the testing of hypotheses with regard to carbohydrate metabolism in physiological and pathological conditions with emphasis on the diabetic state. D2O is administered at a safe, well tolerated dose. In the fasted state hexamethylenetetramine, formed from 6 equivalents of formaldehyde, is used to measure the enrichment of the deuteriums bound to carbons 2,5 and 6 of glucose. Formaldehyde containing the deuterium bound to carbon 6 is formed on periodic acid oxidation of blood glucose. Formaldehyde containing deuterium bound to carbon 5 is formed on oxidation of xylose formed from the glucose. Formaldehyde containing deuterium at carbon 2 is formed by oxidation of ribitol-5-P formed from the glucose. In the fed state, the D2O is given with acetaminophen. Deuterium bound to carbon 2 and 5 of glucose formed from the glucuronic acid moiety of the excreted glucuronide is determined. The fraction of glucose output formed by gluconeogenesis in the fasted state and the fraction of glycogen formation by gluconeogenesis in the fed state, also to the ratio of the enrichment at carbon 5 to that in body water. The carbon 5 to carbon 6 ratio is a measure of the contribution of glycerol to gluconeogenesis and the extend of equilibration of the hydrogens of pyruvate with those in water. Absolute rates of gluconeogenesis in the fasted state are estimated by multiplying the fraction via gluconeogenesis by glucose output measured using tritiated glucose or (6,6-D2) glucose. In the fed state the quantity of glycogen formed is measured using MRI to estimate liver volume and 13CNMR glycogen concentration. In the fasted state MRI and NMR are used to relate estimates of rates of gluconeogenesis to rates of glycogenolysis. Measurements will be made in normal subjects, in subjects who are obese and in NIDDM and MODY subjects. The findings should bear on the role of the liver in producing hyperglycemia in the diabetic. This in turn bears on the design of therapeutic agents and the adequacy of insulin given systemically in returning metabolism, not just blood glucose concentration, to normal. The approach for the first time allows the giving of D2O in safe and convenient doses to obtain adequate labeling in glucose for measurements of the pathways of its formation and conversion to glycogen. Because of the small dose of deuterated water that has to be given and the small amount of glucose that is required for analysis, the approach should be useful in pediatric as well s adult clinical studies.