AMINO ACID REGULATION OF GLUCOSE METABOLISM IN VIVO

体内葡萄糖代谢的氨基酸调节

• 批准号: 3464346
• 负责人: PAUL J FLAKOLL
• 金额: $ 10.38万
• 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/3464346
• 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 酸被广泛用作唯一的营养素，以TPN的形式，以 有严重压力的患者。这引起了相当大的兴趣 葡萄糖与胰岛素之间以及葡萄糖与胰岛素之间的直接相互作用 胰岛素和氨基酸在调节这些动物营养需要中的作用 患者；然而，很少有研究检查两者之间的直接互动 葡萄糖和氨基酸。我的初步数据显示，氨基酸 降低葡萄糖处理率，包括胰岛素依赖型和 不依赖胰岛素，在人和狗身上。它们还暗示氨基酸 钝化胰岛素降低肝脏糖异生的有效性 葡萄糖的产生。氨基酸对葡萄糖的这种“有害”作用 新陈代谢与研究者以往研究的对比(附录) 显示氨基酸对胰岛素抑制胰岛素的“有益”作用 蛋白质分解和促进蛋白质合成。本申请 建议解决葡萄糖和氨基相互作用的影响 酸对糖原沉积和氮素积累的影响如何确定氨基 酸的输注量与TPN溶液中使用的量相似，影响 全身葡萄糖产生率和葡萄糖利用率。这个 研究人员将把重点放在糖原沉积和 分解，以及肌肉和肌肉中蛋白质合成和分解 肝脏。还建议检查输入氨基酸是否 改变肝脏和肌肉中的糖异生或葡萄糖氧化。 研究人员将研究支链和支链的特殊作用 这些溶液的组成中含有成糖氨基酸 新陈代谢改变。调查员将利用禁食4天的狗 已发现代表糖原耗竭状态的模型和 胰岛素抵抗，应激患者需要TPN治疗的特征 营养补充。不管有没有氨基酸，葡萄糖都会 在最初的禁食后4天内输注，在结束时进一步 营养和新陈代谢评估将被记录在案。葡萄糖和氨基 酸动力学将利用同位素技术进行研究。 在调查员实验室建立。将使用器官平衡 检测氨基酸、葡萄糖、尿素和体内氧化作用。这些 因此，研究将确定氨基酸和葡萄糖在体内的相互作用。 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， 可以定义最佳营养方案，最终导致更好的疾病 结果。