This project lies at the interface between nutrition and gastroenterology. It asks how the nutrient update mechanisms of the intestine are adaptively regulated by changes in diet and other conditions. The long-term objectives focus on three questions. 1. What are the patterns of changes in nutrient update with diet changes, pregnancy, and other normal and disease related conditions? 2. What are the mechanisms responsible for each of these patterns? (e.g., change in specific transport system, mucosal mass, or the Na+ gradient). 3. What are the signals for these changes? (e.g., transported solutes themselves, hormones, or pancreaticobiliary secretions).
The specific aims of this proposal are two-fold: 1. How does intestinal update of amino acids (AA's) vary with dietary protein content? In particular, how are each of the major uptake mechanisms for AA's regulated by the distinct roles of protein as a source of calories, nitrogen, and essential AA's? 2. Is nutrient uptake in the adult individual influenced in any irreversible way by that individual's diet shortly after weaning, or by its mother's diet during the gestation and nursing periods? That is, are there any critical-period phenomena in the programming of nutrient uptake mechanism? The main methods to be used will measure tracer uptake; to a much lesser extent, electrophysiological parameters, morphometry, and hormone levels. The project has major health-related implications for: 1. effects of protein malnutrition (kwashiorkor) on amino acid uptake, feeding back onto the malnutrition; 2. health consequences of altered plasma levels of nutrients due to altered intestinal nutrient uptake, resulting in turn from normal conditions such as pregnancy, aging, and changed diet; 3. altered nutrients uptake in post-gastrectomy malabsorption syndrome, short-bowel syndrome, diabetes, and other disease states.
