AMINO ACID REGULATION OF GLUCOSE METABOLISM IN VIVO

体内葡萄糖代谢的氨基酸调节

• 批准号: 2142892
• 负责人: PAUL J FLAKOLL
• 金额: $ 11.44万
• 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/2142892
• 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.

描述（改编自申请人的摘要）：葡萄糖和氨基 酸以 TPN 的形式被广泛用作唯一营养素， 承受严重压力的患者。 这引起了人们的极大兴趣 葡萄糖和胰岛素之间以及葡萄糖和胰岛素之间的直接相互作用 胰岛素和氨基酸调节这些的营养需求 患者;然而，很少有研究探讨两者之间的直接相互作用 葡萄糖和氨基酸。 我的初步数据表明氨基酸 降低葡萄糖处理率，包括胰岛素依赖性和 人和狗不依赖胰岛素​​。 它们还暗示氨基酸 削弱胰岛素降低肝糖异生作用的效果 葡萄糖生产。 氨基酸对葡萄糖的这种“有害”影响 与研究者之前的研究的代谢对比（附录） 显示氨基酸对胰岛素抑制的“有益”作用 蛋白水解和刺激蛋白质合成。 本申请 提出解决葡萄糖和氨基相互作用的影响 酸对糖原沉积和氮积累的影响，以确定氨基酸如何 酸输注量与 TPN 溶液中使用的量相似，会影响 全身葡萄糖生成率和葡萄糖利用率。 这 研究人员将重点关注糖原沉积和糖原沉积的变化 分解，以及肌肉和肌肉中的蛋白质合成和分解 肝。 还建议检查是否输注氨基酸 改变肝脏和肌肉中的肝糖异生或葡萄糖氧化。 研究者将检查支链的特殊作用和 这些溶液的成分中的糖原氨基酸 代谢改变。 调查员将利用禁食 4 天的狗 已发现代表糖原耗尽状态的模型 胰岛素抵抗，压力患者的标志，需要 TPN 营养补充。 含或不含氨基酸的葡萄糖将 初次禁食后注射 4 天，最后进一步注射 营养和代谢评估将被记录下来。 葡萄糖和氨基 将利用成熟的同位素技术来检查酸动力学 在研究人员实验室中建立。 将使用器官天平 检查氨基酸、葡萄糖、尿素和体内的氧化情况。 这些 因此，研究将定义氨基酸和葡萄糖对 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， 可以确定最佳的营养方案，最终改善疾病 结果。