LIPEMIA--CARBOHYDRATE AND GLYCERIDE METABOLISM

脂血症--碳水化合物和甘油酯的代谢

• 批准号: 2609175
• 负责人: GERALD M. REAVEN
• 金额: $ 24.64万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2609175
• 关键词: atherosclerosis; blood lipoprotein metabolism; blood pressure; carbohydrate metabolism; cell cell interaction; clinical research; coronary disorder; coronary vasodilator; cyclic GMP; dietary carbohydrates; dietary lipid; drug adverse effect; glucose tolerance; glycerides; human subject; hypertension; insulin sensitivity /resistance; monocyte; nitric oxide; nutrition related tag; peptide hormone metabolism; saturated fatty acids; vascular endothelium

DESCRIPTION (Adapted from Applicant's Abstract): The long-term objective of this grant has been to define the role played by resistance to insulin-mediated glucose disposal (and the abnormalities related to this fundamental defect) in the genesis of coronary heart disease (CHD). The studies outlined in this proposal will attempt to show that the metabolic abnormalities associated with insulin resistance (Syndrome X) have adverse effects on endothelial vasodilator reactivity and the interaction between monocytes and the endothelium that represent early stages in the process of atherogenesis. Studies will be performed in normal subjects and patients with either impaired glucose tolerance or hypertension, further sub-divided into insulin sensitive and insulin resistant subjects. A variety of experimental variables will be measured at baseline in order to define multiple facets of their glucose, insulin, and lipoprotein metabolism. In addition, we plan to characterize alterations in endothelial function by quantifying nitric oxide and cyclic GMP concentrations, and brachial artery vasodilatory responses to endothelium-dependent and endothelium-independent stimuli. Furthermore, the investigators will perform ex vivo and in vitro studies of determinants of endothelial-monocyte interactions. Following these baseline comparisons, all subjects will begin a 10-week period in which two diets will be consumed, in a randomly assigned, cross-over design. The diets will be similar, with the exception that in one diet carbohydrate will be substituted for saturated fat (CHO), whereas in the other diet primarily mono- and poly-unsaturated fat will be substituted for saturated fat (MF/PF). Based upon previous results, it is known that the abnormalities in glucose, insulin, and lipoprotein metabolism present in insulin resistant subjects will be accentuated by the CHO diet and attenuated by the MF/PF diet, with relatively little change seen in the insulin sensitive subjects. At the end of each dietary period, all baseline tests will be repeated. The results of the measurements following dietary manipulation will provide an even more sensitive means to further evaluate the effect of differences in insulin resistance, and its associated metabolic abnormalities, on brachial artery vasodilator responses and factors regulating endothelial-monocyte interaction, as modified by variations in glucose tolerance status and blood pressure. As such, this study will provide considerable new knowledge relevant to the link between Syndrome X and atherogenesis.

描述（改编自申请人的摘要）： 这一补助金是为了确定抵抗运动所发挥的作用， 胰岛素介导的葡萄糖处置（以及与此相关的异常 冠心病（CHD）的发病机制中的基本缺陷）。 的 这项提案中概述的研究将试图表明， 与胰岛素抵抗相关的异常（X综合征）具有不利的 对内皮血管舒张反应性的影响以及 单核细胞和内皮细胞，代表在这个过程中的早期阶段， 动脉粥样硬化 研究将在正常受试者和患者中进行 葡萄糖耐量受损或高血压，进一步细分 分为胰岛素敏感和胰岛素抵抗的受试者。 各种 将在基线测量实验变量，以确定 葡萄糖、胰岛素和脂蛋白代谢的多个方面。 在 此外，我们计划通过以下方法来表征内皮功能的改变： 定量一氧化氮和环GMP浓度，以及肱动脉 内皮依赖性和非内皮依赖性血管舒张反应 刺激。 此外，研究者将进行离体和体外研究， 内皮细胞-单核细胞相互作用的决定因素的研究。 以下 在这些基线比较中，所有受试者将开始10周， 哪两种饮食将被消耗，在一个随机分配，交叉设计。 饮食将是相似的，除了在一个饮食碳水化合物 将取代饱和脂肪（CHO），而在其他饮食 主要是单不饱和脂肪和多不饱和脂肪将取代饱和脂肪， 脂肪（MF/PF）。 根据之前的结果，可以知道 葡萄糖、胰岛素和脂蛋白代谢异常， 胰岛素抵抗受试者将因CHO饮食而加重， 通过MF/PF饮食减弱，在 胰岛素敏感性受试者。 在每个饮食期结束时，所有基线 将重复测试。 饮食后的测量结果 操纵将提供一个更加敏感的手段，以进一步评估 胰岛素抵抗的差异及其相关的 代谢异常，肱动脉血管舒张反应， 调节内皮细胞-单核细胞相互作用的因子，经 葡萄糖耐量状态和血压的变化。 因此，这 研究将提供与以下联系相关的大量新知识 X综合征与动脉粥样硬化