Total parenteral nutrition (TPN) is a vital feeding technique for individuals who cannot tolerate oral nutrition. The anabolic response to TPN is often suboptimal due to alterations in the nutritional-hormonal regulation of growth and metabolism. Insulin-like growth factor I (IGF-I) mediates the actions of growth hormone (GH), causes glucose uptake, and is anabolic in the gut and immune system. IGF-I production and action are regulated by nutritional, hormonal, and metabolic status. The long term goal of this research is to understand the mechanisms by which the nutrient composition of TPN and the GH/IGF-I system interact to design TPN protocols, i.e., combinations of nutrients and growth factors, that will optimize tissue repair and growth. The four specific aims are to determine: 1)the dose-response relationship for the anabolic effects of IGF-I, GH and the combination of these growth factors when given concurrently with TPN; 2)if increased body growth due to administration of IGF-I plus GH during TPN is secondary to increased protein synthesis and increased carbohydrate oxidation; 3)the relationship between parenteral fat emulsions, gut immune function and the known ability of IGF-I to attenuate TPN-induced gut atrophy; and 4)how the nonprotein source of parenteral energy glucose vs. fat) and the total amount of parenteral energy regulate hepatic IGF-I synthesis, and the anabolic response to exogenous IGF-I and its analogues that do not bind IGF binding proteins. TPN feeding studies will be conducted in rats given surgical stress or dexamethasone treatment; IGF-I will be confused with the TPN solution. IGF-I system responses will be assessed by determining: serum concentrations of GH, IGF-I, IGF binding proteins, insulin, and glucose; tissue abundance of mRNAs for IGF-I, IGF-I and GH receptors, and IGF binding proteins; and by conducting receptor binding and tyrosine kinase studies. Anabolic response will be assessed by determining body weight and composition, nitrogen balance, the fractional rate of protein synthesis and energy expenditure.
Showing the most recent 10 out of 39 publications
