GLUCONEOGENESIS IN LOW BIRTH WEIGHT INFANTS RECEIVING TOTAL PARENTERAL NUTRITION

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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.