COMPARATIVE STUDIES OF INTRACELLULAR GLUCOSE METABOLISM

细胞内葡萄糖代谢的比较研究

• 批准号: 3462900
• 负责人: Robert Roy Henry
• 金额: $ 7.86万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3462900
• 关键词: artificial endocrine pancreas; biopsy; blood chemistry; calorimetry; cellular pathology; glucose metabolism; glucose transport; glycogen synthase; glycolysis; human subject; hyperglycemia; hyperinsulinism; inborn carbohydrate metabolism disorder; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; obesity; striated muscles

The peripheral metabolism of glucose involves movement across the cell membrane of tissues followed by intracellular processing via oxidative and non-oxidative pathways. Peripheral insulin resistance is a well documented abnormality in obesity and Type II diabetes mellitus (NIDDM) and is due primarily to a post-receptor (post-binding) once it enters the cells and if abnormalities in intracellular metabolism might play a role in the insulin resistance of these disorders. Due to insulin resistance, at any given level of serum insulin and glucose, lower rates of glucose disposal result in reduced rates of glucose flux through intracellular pathways compared to non-diabetic nonobese individuals. Because of this, accurate comparisons of intermediary metabolism or delineation of any intrinsic intracellular metabolic defects independent of the decreased glucose disposal rates are difficult to make. In these studies, we plan to evaluate the effects of obesity and NIDDM on in vivo and in vitro intracellular glucose metabolism to determine whether intrinsic defects of intracellular glucose metabolism exist in NIDDM and/or obesity or whether these defects are merely secondary to the decreased rate of glucose entry into the cell. We propose to accomplish this by using levels of hyperinsulinemia and hyperglycemia designed to attain similar rates of in vivo glucose disposal in comparably matched groups of non-obese, obese and NIDDM subjects. To conduct these studies the insulin-glucose clamp technique will be employed to measure glucose uptake rates in conjunction with simultaneous computerized open circuit indirect calorimetry to quantitate oxidative and non-oxidative glucose metabolism (NOGM). To determine whether corresponding changes are occurring in the primary peripheral target organ, samples or quadriceps femoris muscle will be obtained by needle biopsy during these studies for determination of glycolytic pathway metabolites and the rate limiting enzyme for glycogen synthesis, glycogen synthase. It is anticipated that these studies will delineate the importance of insulin, glucose and overall glucose disposal on the metabolic fate of glucose and indicate whether an intrinsic defect(s) in the intermediary metabolic handling of glucose exists in obesity and NIDDM.

葡萄糖的外周代谢涉及跨过 组织的细胞膜，然后通过细胞内处理 氧化途径和非氧化途径。 外周胰岛素 抵抗力是肥胖和 II 型肥胖症中一个有据可查的异常现象 糖尿病（NIDDM），主要是由于后受体 （结合后）一旦进入细胞并且如果异常 细胞内代谢可能在胰岛素中发挥作用 这些疾病的抵抗力。 由于胰岛素抵抗，任何时候 给定血清胰岛素和血糖水平，血糖发生率较低 处置导致葡萄糖通量降低 与非糖尿病非肥胖者相比的细胞内途径 个人。 正因为如此，中介的准确比较 任何内在细胞内代谢的代谢或描述 与葡萄糖处理率降低无关的缺陷是 很难制作。 在这些研究中，我们计划评估 肥胖和 NIDDM 对体内和体外细胞内的影响 葡萄糖代谢以确定是否存在内在缺陷 NIDDM 和/或肥胖中存在细胞内葡萄糖代谢或 这些缺陷是否仅仅是降低率的次要问题 葡萄糖进入细胞的过程。 我们建议通过以下方式实现这一目标 使用高胰岛素血症和高血糖水平设计 在相当的情况下达到相似的体内葡萄糖处理率 非肥胖、肥胖和 NIDDM 受试者的匹配组。 进行 这些研究将采用胰岛素-葡萄糖钳夹技术 结合同时测量葡萄糖摄取率 计算机开路间接量热法定量 氧化和非氧化葡萄糖代谢（NOGM）。 到 判断是否发生相应的变化 主要外周靶器官、样本或股四头肌 在这些研究期间将通过针吸活检获得肌肉 糖酵解途径代谢物及其速率的测定 糖原合成的限制酶，糖原合酶。 这是 预计这些研究将阐明的重要性 胰岛素、葡萄糖和总体葡萄糖处理对代谢命运的影响 葡萄糖并指出是否存在内在缺陷 葡萄糖的中间代谢处理存在于肥胖和 NIDDM。