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. Hyperglycemia is frequently encountered when sick newborn infants receive TPN providing glucose exceeding the infant normal glucose turnover rate. Recent studies in critically ill children and adults have demonstrated that hyperglycemia was associated with increased mortality. Since sick newborns, particularly those with very low birth weight also constitute a high-risk population, preventing hyperglycemia without compromising their energy intake, may reduce their risk of an adverse outcome. To accomplish this goal requires detailed knowledge about potential factors involved in the development of hyperglycemia (regulation of glucose production, gluconeogenesis, glycogenolysis, glucose utilization; and insulin secretion and insulin resistance), and the mechanisms by which e.g. insulin infusion and reduced glucose infusion rates affect glucose metabolism to reduce blood glucose. The protocols described below represent the first part of a larger planned project to address these issues and test the hypotheses that: 1. Rates of gluconeogenesis do not change in response to a decrease in concentrations of glucose and insulin resulting from a reduction of the rate of glucose infusion to 3 mg/kg min; 2. Infusion of insulin will a) not acutely suppress rates of gluconeogenesis; b) increase glucose utilization in proportion to body weight; c) increase protein synthesis. These studies will improve our insight into the regulation of glucose production from gluconeogenesis and glycogenolysis and the mechanisms by which insulin infusion affects glucose and protein metabolism. A clear understanding of the mechanisms that control glucose homeostasis in the extremely low birth weight infant will permit us to develop evidence based strategies to maintain euglycemia while providing appropriate energy intak
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