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.

葡萄糖的周围代谢涉及在整个 组织的细胞膜，然后通过细胞内处理 氧化和非氧化途径。 外围胰岛素 抗性是肥胖和II型的良好文献异常 糖尿病（NIDDM），主要归因于受体后者 （结合后）一旦进入细胞，否则 细胞内代谢可能在胰岛素中起作用 这些疾病的抵抗。 由于胰岛素抵抗，任何 给定血清胰岛素和葡萄糖的水平，葡萄糖的速率较低 处置导致葡萄糖通量降低 与非糖尿病非肥胖相比，细胞内途径 个人。 因此，中介的准确比较 任何内在的细胞内代谢的代谢或描述 与葡萄糖处置率降低无关的缺陷为 难以制作。 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 葡萄糖代谢以确定固有缺陷是否存在 NIDDM和/或肥胖症或肥胖症中存在细胞内葡萄糖代谢或 这些缺陷是否仅次于降低率 葡萄糖进入细胞。 我们建议通过 使用高胰岛素血症和高血糖的水平 达到相似的体内葡萄糖处置速率 匹配的非肥胖，肥胖和NIDDM受试者组。 进行 这些研究将采用胰岛素 - 葡萄糖夹技术 同时测量葡萄糖摄取速率 计算机开放电路间接量热法以定量 氧化和非氧化葡萄糖代谢（NOGM）。 到 确定是否在 主要的外围靶器官，样品或股四头肌股骨 在这些研究期间，将通过针头活检获得肌肉 糖酵解途径代谢物的测定和速率 限制用于糖原合成，糖原合酶的酶。 这是 预计这些研究将描述 代谢命运上的胰岛素，葡萄糖和总葡萄糖处置 葡萄糖并指示是否固有缺陷 肥胖症中存在葡萄糖的中介代谢处理 NIDDM。