The likelihood of future widespread use of glutamine supplementation in infants and adults begs a better understanding of basic mechanisms of action. Our previous studies point to nutritional processes in the intestine as playing a major role in the health benefits of glutamine. The four hypotheses to be tested will focus on the intestinal effects of glutamine and answer: 1) What is the relative nutritional value of glutamine when presented apically or basally to intestinal epithelial cells? 2) Can glutamate effectively substitute for glutamine 3) Can downstream metabolites of glutamine (e.g., nucleotides, hexosamines and other amino acids) substitute for glutamine in intestinal epithelium? 4) Will the substance identified in the cell culture experiments from aims 1-3 be valuable in vivo? Our approach will employ intestinal proliferating and differentiating epithelial cells grown in Matrigel on transwell plates, stable isotopic tracers for metabolic labeling studies and an in vivo rat infant """"""""pup in the cup"""""""" model that can be used to manipulate feeding regimens. These investigations will provide, in a timely fashion, information to help interpret the outcomes of large ongoing clinical trials and to determine whether positive outcomes actually are mediated directly by nutritional effects on the intestine. Considering the technical limitations in administering glutamine (degradation in aqueous solutions), these studies will suggest alternatives providing the same benefits in a safer and more practical manner.
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