AMINO ACID REGULATION OF GLUCOSE METABOLISM IN VIVO

体内葡萄糖代谢的氨基酸调节

• 批准号: 3464347
• 负责人: PAUL J FLAKOLL
• 金额: $ 10.9万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3464347
• 关键词: aminoacid metabolism; disease /disorder model; dogs; fasting; glucose metabolism; glycogenesis; glycogenolysis; hormone regulation /control mechanism; insulin; insulin sensitivity /resistance; isotope dilution method; liver metabolism; muscle metabolism; nutrition related tag; protein biosynthesis; proteolysis

DESCRIPTION (Adapted from the applicant's abstract): Glucose and amino acids are widely utilized as sole nutrients, in the form of TPN, to patients with severe stress. This has generated considerable interest in the direct interactions between glucose and insulin as well as between insulin and amino acids in modulating nutrient requirements of these patients; few studies, however, examined the direct interaction between glucose and amino acids. My preliminary data indicate that amino acids decrease the rates of glucose disposal, both insulin-dependent and insulin-independent, in man and dogs. They also imply that amino acids blunt the effectiveness of insulin on lowering hepatic gluconeogenesis and glucose production. This "detrimental" effect of amino acids on glucose metabolism contrast with the investigators previous studies (Appendix) showing a "beneficial" effect of amino acids on insulin's inhibition of proteolysis and stimulation of protein synthesis. The present application proposes to address the influence of the interaction of glucose and amino acids on glycogen deposition and nitrogen accretion to determine how amino acid infusions, in amounts similar to those used in TPN solutions, affect whole body rates of glucose production and glucose utilization. The investigator will focus on the alterations in glycogen deposition and breakdown, as well as on protein synthesis and breakdown in both muscle and liver. It is also proposed to examine whether the infusion of amino acids alters hepatic gluconeogenesis or glucose oxidation in liver and muscle. The investigator will examine the special role of branched chain and glycogenic amino acids in the composition of these solutions on these metabolic alterations. The investigator will utilize the 4 day fasted dog model which has been found to represent a state of glycogen-depletion and insulin resistance, hallmarks of the stressed patient requiring TPN for nutritional supplementation. Glucose with or without amino acids will be infused for 4 days following the initial fast at the end of which further nutritional and metabolic assessment will be documented. Glucose and amino acid kinetics will be examined utilizing isotopic techniques that are well established in the investigators laboratory. Organ balances will be used to examine amino acid, glucose, urea and oxidation by the body. These studies will thereby define interactions of amino acids and glucose on the disposition of protein and glycogen stores. Hence, by defining the mechanism responsible for the interaction of these major metabolites, optimal nutritional regimes can be defined culminating in better disease outcomes.

性状（改编自申请人摘要）：葡萄糖和氨基 酸被广泛用作唯一的营养素，以TPN的形式， 有严重压力的病人。 这引起了相当大的兴趣， 葡萄糖和胰岛素之间的直接相互作用以及 胰岛素和氨基酸在调节这些营养需求 患者;然而，很少有研究检查了 葡萄糖和氨基酸。 我的初步数据显示氨基酸 降低葡萄糖处置率，包括胰岛素依赖型和 胰岛素非依赖性，在人和狗中。 这也意味着氨基酸 减弱胰岛素降低肝细胞生成的有效性， 葡萄糖生产。 氨基酸对葡萄糖的这种“有害”作用 与研究者先前研究的代谢对比（附录） 显示了氨基酸对胰岛素抑制胰岛素分泌的“有益”作用。 蛋白水解和刺激蛋白质合成。 本申请 建议解决葡萄糖和氨基的相互作用的影响， 氨基酸对糖原沉积和氮积累的影响，以确定氨基酸 与TPN溶液中使用的量相似的酸输注影响 全身葡萄糖产生率和葡萄糖利用率。 的 研究者将重点关注糖原沉积的变化， 分解，以及蛋白质的合成和分解，在肌肉和 肝脏 还建议检查是否输注氨基酸 改变肝脏和肌肉中的肝细胞生成或葡萄糖氧化。 研究人员将研究支链的特殊作用， 这些解决方案的组成中的糖原氨基酸对这些 代谢改变 研究者将使用禁食4天的犬 已经发现该模型代表糖原耗尽的状态， 胰岛素抵抗，需要TPN的应激患者的标志， 营养补充。 含或不含氨基酸的葡萄糖将 在初始禁食后输注4天， 将记录营养和代谢评估。 葡萄糖和氨基 酸动力学将利用同位素技术进行检查， 在研究者实验室中建立。 将使用器官平衡 检测氨基酸、葡萄糖、尿素及体内氧化作用。 这些 因此，研究将确定氨基酸和葡萄糖对 蛋白质和糖原储存的处置。 因此，通过定义 负责这些主要代谢物相互作用的机制， 最佳的营养方案可以被定义为最好的疾病 结果。