UNIQUE PROTEIN AND ENERGY DEMANDS OF SICKLE CELL DISEASE

镰状细胞病独特的蛋白质和能量需求

• 批准号: 6128952
• 负责人: PAUL J FLAKOLL
• 金额: $ 9.26万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6128952
• 关键词: basal metabolism; bioenergetics; caloric dietary content; calorimetry; clinical research; glucose clamp technique; hormone regulation /control mechanism; human subject; insulin; muscle metabolism; nutrition; nutrition related tag; protein metabolism; sickle cell anemia

Homozygous sickle cell disease (HbSS) is a major health problem throughout the United States and the world that results in vaso- occlusive events, a variety of secondary disease complications, and a reduced life expectancy. HbSS is a genetic disorder Characterized by the sickling of red blood cells (RBC) due to the replacement of glutamic acid with valine in position 6 on the beta chains of hemoglobin. As a result of this structural change, the life span of the RBC is greatly reduced from the normal 120 days to approximately 10 days. The sickling of RBCs leads to a chronic anemia and increased RBC catabolism and synthesis. These physiological perturbations have the potential to promote increased energy expenditure, increased protein breakdown and synthesis, increased anaerobic metabolism, and altered insulin action. Each of these metabolic derangements is capable of altering specific substrate oxidation and increasing protein and energy demands. The overall aim of the proposed research is to determine the impact of HbSS on whole-body and skeletal muscle nutrient metabolism and demands. Two separate protocols have been designed to identify the mechanisms by which protein and energy demands are increased during HbSS. These protocols will 1) define how changes in nutrient metabolism during HbSS alter energy metabolism basally and during the simulated ingestion of a meal, 2) determine whether increased protein and/or energy availability improves protein homeostasis in HbSS patients 3) identify how the protein synthetic demands of RBCs and other specific tissues impact upon the protein and energy requirements in HbSS, and 4) define the influence of HbSS on insulin-mediated nutrient utilization. Therefore, the protocols will focus on events associated with post-absorptive, meal-related, and insulin-mediated metabolism. These experiments will use isotopic tracer techniques, indirect calorimetry, nutrient infusions, and euglycemic-hyperinsulinemic clamps in HbSS patients. When combined, the proposed protocols will enhance our understanding of how HbSS alters protein and energy metabolism and will identify mechanisms for these alterations. The contribution of HbSS to health care costs is significant, and the knowledge gained from these studies will enable us to better understand the various metabolic processes associated with HbSS. This knowledge will assist in the design of appropriate nutritional regimens, thereby culminating in better disease outcomes.

纯合镰状细胞病（HBSS）是一个主要的健康问题 在整个美国和世界各地，导致了血管 闭塞事件，各种继发性疾病并发症以及 预期寿命降低。 HBSS是一种特征的遗传疾病 由于替换了红细胞（RBC）的恶心 谷氨酸在位于位置6的谷氨酸在β链上的位置6 血红蛋白。由于这种结构性变化， RBC大大降低了120天 10天。 RBC的恶心导致慢性贫血和 RBC分解代谢和合成增加。这些生理 扰动有可能促进能量增加 支出，蛋白质分解增加和合成，增加 厌氧代谢，改变了胰岛素作用。每个 代谢异常能够改变特定的底物 氧化和蛋白质和能量需求的增加。总体 拟议研究的目的是确定HBSS对 全身和骨骼肌肉营养代谢和需求。 已经设计了两个单独的协议来确定 蛋白质和能量需求增加的机制 在HBSS期间。这些协议将1）定义养分的变化如何 HBSS期间的代谢基本改变了能量代谢 一餐的模拟摄入，2）确定是否增加 蛋白质和/或能量可用性可改善蛋白质稳态 HBSS患者3）确定蛋白质合成的需求 RBC和其他特定组织对蛋白质和能量的影响 HBSS和4）定义HBS对 胰岛素介导的营养利用率。因此，协议将 专注于与饮食后，与进餐相关的事件和 胰岛素介导的代谢。 这些实验将使用同位素 示踪技术，间接量热法，营养输注和 HBSS患者中的Eugpymemic-Hyperinsulinemic夹具。 什么时候 合并，提议的协议将增强我们对 HBSS如何改变蛋白质和能量代谢，并将确定 这些改变的机制。 HBS对健康的贡献 护理费用很大，并且从这些研究中获得的知识 将使我们能够更好地了解各种代谢过程 与HBS相关。这些知识将有助于设计 适当的营养方案，从而提高 疾病结果。