GLUCONEOGENESIS IN LOW BIRTH WEIGHT INFANTS RECEIVING TOTAL PARENTERAL NUTRITION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在过去的几十年里，对早产儿管理的改进，特别是心肺治疗的进步，使死亡率大大降低。然而，我们对它们的代谢需求和宏量营养素需求的了解仍然有限。VLBW婴儿易患低血糖；因此，为了提供足够的热量和防止低血糖，作为标准全肠外营养（TPN）的一部分，常规以高速率（60 mmol/kg min，是这些婴儿测量的葡萄糖周转率的两倍）输注葡萄糖，这经常导致高血糖。与低血糖一样，高血糖也会对VLBW婴儿的预后产生显著的短期和长期不良影响。该项目的具体重点是确定标准全肠外营养中提供的底物对糖原分解和糖异生（GNG）产生葡萄糖和葡萄糖利用的个体和集体作用。这些研究将确定：a.接受TPN的正常血糖的VLBW婴儿是否完全抑制了他们的葡萄糖生成，而那些高血糖的婴儿是否完全抑制了葡萄糖生成和/或降低了葡萄糖利用；b.当VLBW婴儿以降低的速率（17 mmol/kg）提供葡萄糖时。分钟):1。静脉注射脂质（内脂质）是否增加GNG和葡萄糖的产生，如果是这样，这是通过b-氧化为GNG提供能量或提供甘油作为3碳前体的结果？2. 甘油是否以剂量依赖性方式增加VLBW婴儿的GNG和葡萄糖生成3. 静脉注射氨基酸溶液（TrophAmine）和/或糖异生氨基酸，谷氨酰胺和丙氨酸，是否会增加GNG和葡萄糖的产生；和4。胰高血糖素是否会增加GNG和内源性和外源性底物来源的葡萄糖产量。最终目的是利用这些信息设计成分（底物和可能的激素）的替代混合物，通过利用婴儿的糖异生途径，同时提供足够的底物来维持正常的生长和发育，从而降低这些婴儿低血糖和高血糖的风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the last decades, improvements in the management of very premature infants, particularly, advances in cardio respiratory treatment, have resulted in a significantly decreased mortality rates. However, our knowledge about their metabolic needs and macronutrient requirements is still limited. VLBW infants are susceptible to hypoglycemia; thus, to provide sufficient calories and to prevent hypoglycemia, glucose is routinely infused at high rates ('bb 60 mmol/kg min twice that of measured glucose turnover rates in these infants) as part of standard total parenteral nutrition (TPN) which frequently results in hyperglycemia. Like hypoglycemia, hyperglycemia can have significant short and long term adverse impact on the outcome of VLBW infants. The specific focus of this project is to determine the individual and collective roles of the substrates provided in standard total parenteral nutrition on glucose production from glycogenolysis and gluconeogenesis (GNG) and glucose utilization. These studies will determine: a. Whether VLBW infants receiving TPN who are normoglycemic suppress their glucose production completely and those who are hyperglycemic have incomplete suppression of glucose production and/or reduced glucose utilization; b. When VLBW infants are supplied glucose at a reduced rate (17 mmol/kg.min): 1. Do i.v. lipids (Intralipid) increase GNG and glucose production and if so is this the result of providing energy for GNG through b-oxidation or providing glycerol as a 3-carbon precursor; 2. Whether glycerol increases GNG and glucose production in a dose dependent fashion in VLBW infants; 3. Whether i.v. amino acid solution (TrophAmine) and/or the gluconeogenic amino acids, glutamine and alanine, will increase GNG and glucose production; and 4. Whether glucagon will increase GNG and glucose production from endogenous and exogenous substrate sources. The ultimate aim is to utilize this information in designing alternative mixtures of constituents (substrates and possibly hormones) which will decrease the risk of both hypo- and hyperglycemia in these infants, by utilizing the infants' gluconeogenic pathway, while providing sufficient substrate to sustain normal growth and development.