Nutrition, Infection and Hepatic Carbohydrate Metabolism

外源性营养物质的代谢会因感染而显著改变。 在接受营养支持时发生感染的个体的标志之一是高血糖症。 也有一个伴随的代谢率的增加和外源性营养素无法抑制氮排泄，脂肪氧化和增加的脂肪生成的增加。 高血糖症的主要原因是由于身体不能有效地处理外源性葡萄糖。 特定组织在导致损伤中的作用尚不清楚。根据我们的研究，在接受全胃肠外营养的正常动物中，肝脏是葡萄糖处置的主要部位（约占输注的外源性葡萄糖的50%），肝脏对葡萄糖的摄取受到感染的显著抑制。 以及周围组织处理葡萄糖碳。还已知营养支持途径（肠内或胃肠外）改变了肝脏在急性环境中摄取葡萄糖的能力，但这种益处不会长期持续。该提案的第一个目标是确定肠内和胃肠外营养支持的正常适应的时间过程和机制。 第二个目标是确定葡萄糖输送途径是否可以长期调节肝脏葡萄糖摄取，以及是否受感染影响。 第三个目标是确定慢性高胰岛素血症、高胰高血糖素血症和高血糖症如何相互作用以调节感染期间肝脏葡萄糖摄取。实验将在接受持续营养支持的长期插管清醒犬中进行。 将使用示踪剂和动静脉差异技术的组合评估肝脏葡萄糖代谢（单向肝脏葡萄糖摄取和产生、葡萄糖氧化）。此外，我们将同时评估肢体葡萄糖摄取和处置。 虽然以前的工作一直在研究全身葡萄糖代谢对感染的反应，但我们将能够独特地直接研究单个器官（肝脏肌肉）在感染诱导的营养物质分布调节中所起的作用。 通过使用药理学技术（生长抑素，磷酸化酶a抑制），我们不仅可以确定造成损害的因素，而且还可以确定其机制。

The metabolism of exogenous nutrients administered is markedly altered by infection. One of the hallmarks of an individual that develops an infection while receiving nutritional support is hyperglycemia. There is also a concomitant increase in the metabolic rate and the inability of exogenous nutrients to suppress the elevated nitrogen excretion, fat oxidation and increased gluconeogenesis. The primary cause of the hyperglycemia is due to the inability of the body to efficiently dispose of the exogenous glucose. The role of specific tissues in contributing to the impairment is unclear. Based upon our studies the liver is a major site of glucose disposal (approximately 50 percent of the exogenous glucose infused) in normal animals receiving total parenteral nutrition and the uptake of glucose by the liver is markedly suppressed by infection. And peripheral tissues dispose of the glucose carbon. It is also known that the route of nutrient support (enteral or parenteral) alters the ability of the liver to take up glucose in the acute setting but this benefit does not persist chronically. The first goal of the proposal is to determine the time course of and the mechanism for the normal adaptation to nutritional support given enterally and parenterally. The second goal is to determine if the route by which glucose is delivered can chronically regulate liver glucose uptake and if it is affected by infection. The third goal to determine how chronic hyperinsulinemia, hyperglucagonemia and hyperglycemia interact to regulate liver glucose uptake during infection. Experiments will be carried out in chronically catheterized conscious dogs receiving continuous nutritional support. Hepatic glucose metabolism (unidirectional hepatic glucose uptake and production, glucose oxidation) will be assessed using a combination of tracer and arterio-venous difference techniques. In addition we will simultaneously assess limb glucose uptake and disposal. While previous work has been examining the response of whole body glucose metabolism to infection, we will be uniquely able to directly examine the role that individual organs (liver muscle) plays in the infection induced modulation of nutrient disposition. And by using Pharmacological techniques (somatostatin, phosphorylase a inhibition) we can not only determine the factors responsible for the impairment but we will be able to determine their mechanism as well.