The significance of the maintenance of body protein balance is well recognized, since losses of more than 10 percent of body protein contribute significantly to morbidity and debility in hospitalized patients. The overall objective of this proposal is to examine the hypothesis that exogenous insulin-like growth hormone factor I (IGF-I) could function in a restorative capacity to mitigate or reverse these catabolic trends in the presence of adequate protein-calorie repletion. Studies will utilize isotope tracer methodology, indirect calorimetry and classical body nitrogen and fat measurements to explore the anabolic role of exogenous IGF-I, combined with nutritional support, in increasing glucose and energy utilization and preserving body protein in an acute stress animal model induced by administration of cytokines and endotoxin, and in a chronic stress model simulated by continuous infusion of cytokines and endotoxin for 6 days and by the experimental tumor-bearing animal. Flow cytometric analysis and cell size differentiation will be employed to explore the morphological and functional alterations in relation to nutrients and IGF-I administration, including changes in liver size and the potential preservation of gut mucosa in stressed animals receiving TPN and IGF-I. Moreover, the effects of IGF-I given on a chronic basis on tumor growth will also be examined.
The specific aims of the proposal are: 1) To determine the effects of exogenous IGF-I on energy and glucose metabolism during acute stress conditions induced by cytokines or endotoxin; 2) To determine the effects of exogenous IGF-I on protein metabolism at the whole body level and in individual organs in acute and chronic catabolic animal model; 3) To examine the relationship between the serum IGF level and changes in protein turnover with infusion of cytokines or endotoxin; 4) To determine the effects of IGF-I on protein metabolism of host and tumor tissue in a tumor-bearing animal with long- term parenteral feeding. Completion of these studies will further add to our understanding of the nutritional factors which influence body protein and energy status and of the impact of body composition changes on the integrity of protein metabolism and protein-energy interactions during stress. Data obtained from this project would be expected to be a substantial clinical value in limiting morbidity and mortality in the critically ill patients.
