Carbohydrate and Protein Metabolic Pathways

描述(申请人提供)：碳水化合物、蛋白质和脂肪 异常是糖尿病的特征。长期目标是 开发和应用新方法，极大地促进了对这些问题的理解 生理和病理中的代谢过程及其调控 在人类，特别是在糖尿病中的状态。利用2H2O的优势 以量化所遵循的路径。方法已经被引入，用于 碳水化合物和脂肪。主要的新目标是开发和应用一种方法来 量化蛋白质新陈代谢。碳水化合物的定量方法 新陈代谢也将进一步延长。然后，重点放在1)量化上 蛋白质合成和蛋白质分解；2)对葡萄糖生产的贡献 其在糖尿病中的增加与糖尿病的程度有关 高血糖和3)同时肝糖原合成和 肝功能衰竭，称为糖原循环，这可能有助于解释肝脏功能下降 在2型糖尿病中发现糖原含量并加剧高血糖 葡萄糖摄入。具体目标有四个：1)开发和应用一种方法 为了量化转醛醇酶反应对估计 糖异生作用；2)评估一种使用葡萄糖的方法的有效性 同分异构体，作为一种简单的方法被引入来测量 糖异生作用，与使用2H2O进行比较；3)开发一种方法 通过测量在进食状态下的糖原循环以及 肝糖原沉积率对葡萄糖摄入量的影响，糖原的多少 是由葡萄糖直接形成的，有多少是由三个碳化合物形成的，以及 有多少糖原被重新转化为糖原，即糖原循环； 4)发展了一种从蛋白质标记估计蛋白质合成的方法 通过2H2O，以及由于失去该标记而引起的蛋白质降解。这一点的初步应用 方法将肾功能衰竭患者进行血液透析，其中 摄入的2H2O可以通过透析来清除，以便在丢失结合后很容易地去除 不连续合成标记蛋白质的标记。应用程序首先发送到 肾衰竭状态是在认识到肾病是一种主要的 糖尿病患者的并发症和一种简单的治疗方法的潜在益处 评价不同治疗方法对慢性阻塞性肺疾病蛋白质动力学的影响 那是一种状况。

DESCRIPTION (Provided by applicant): Carbohydrate, protein and lipid abnormalities characterize diabetes mellitus. Long-term objectives are to develop and apply novel methods significantly advancing understanding of those metabolic processes and their regulation in physiological and pathological states in human, and particularly in diabetes. Advantage is taken of 2H2O use to quantitate the pathways followed. Methods have been introduced for carbohydrate and lipid. The major new goal is to develop and apply a method for quantitating protein metabolism. The method for quantitating carbohydrate metabolism will also be further extended. Focus then is on 1) the quantitation of protein synthesis and proteolysis; 2) the contribution to glucose production of gluconeogenesis whose increase in diabetes has been related to the degree of hyperglycemia and 3) the extent of simultaneous hepatic glycogen synthesis and breakdown, called glycogen cycling, which could help explain decreased liver glycogen content found in type 2 diabetes and exacerbate hyperglycemia on glucose ingestion. There are 4 specific aims: 1) To develop and apply a method for quantitating the extent transaldolase reactions contribute to estimates of gluconeogenesis; 2) To evaluate the validity of a method using glucose isotopomers, introduced as a simple method to measure the contribution of gluconeogenesis, in comparison with 2H2O use; 3) To develop a method for quantitating glycogen cycling in the fed state by measuring, along with the rate of hepatic glycogen deposition on glucose intake, how much of the glycogen is formed directly from the glucose, how much from three carbon compounds, and how much from glycogen that is reconverted to glycogen, i.e. glycogen cycling; 4) To develop a method to estimate protein synthesis from labeling of protein by 2H2O, and proteolysis from loss of that label. Initial application of this method will be to renal failure patients undergoing hemodialysis, in whom ingested 2H2O can be removed by dialysis to readily follow loss of incorporated label without continued synthesis of labeled protein. Application first to the renal failure state is done with recognition that nephropathy is a major complication in the diabetic and the potential benefit of a simple method for evaluating the effects of the therapeutic approaches on protein dynamics in that condition.