This project lies at the interface between nutrition and gastroenterology. It asks how the nutrient uptake mechanisms of the intestine are adaptively regulated. The objectives focus on three questions. 1. What are the patterns of changes in nutrient uptake with diet changes, pregnancy, and other normal and disease-related conditions? 2. What are the mechanisms responsible for these changes? 3. What are the signals for these changes? The specific aims are four-fold: 1. What dietary conditions yield maximal induction of each of the four main Na+-dependent amino acid transporters? This study will guide attempts to isolate transporters and to understand inducing signals. 2. Does substrate-dependent induction of transporters take place only in differentiating crypt cells, or in mature enterocytes as well? 3. What are the patterns, triggering signals, functional significance, mechanisms, and possible role as digestive bottlenecks, for the changes in transporters during ontogenetic development? 4. By what mechanisms does experimental diabetes alter nutrient absorption by the intestine? The main methods to be used measure tracer uptake, intestinal morphometry, and transporter site number. The project has health-related implications for: 1. the dietary role of amino acids, not only as essential nutrients but also as inducers of absorption of other nutrients; 2. health consequences of altered plasma levels of nutrients due to altered intestinal nutrient uptake; 3. altered nutrient uptake in diabetes and other disease states.
