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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD038954-01A2
Application #
6197477
Study Section
Nutrition Study Section (NTN)
Program Officer
Grave, Gilman D
Project Start
2000-08-10
Project End
2004-06-30
Budget Start
2000-08-10
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$209,029
Indirect Cost
Name
University of Florida
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Neu, Josef; Mihatsch, Walter (2012) Recent developments in necrotizing enterocolitis. JPEN J Parenter Enteral Nutr 36:30S-5S
Li, Nan; Neu, Josef (2009) Glutamine deprivation alters intestinal tight junctions via a PI3-K/Akt mediated pathway in Caco-2 cells. J Nutr 139:710-4
Neu, Josef; Li, Nan (2007) Pathophysiology of glutamine and glutamate metabolism in premature infants. Curr Opin Clin Nutr Metab Care 10:75-9
Liboni, Kellym C; Li, Nan; Scumpia, Philip O et al. (2005) Glutamine modulates LPS-induced IL-8 production through IkappaB/NF-kappaB in human fetal and adult intestinal epithelium. J Nutr 135:245-51
Neu, Josef; Chen, Mike; Beierle, Elizabeth (2005) Intestinal innate immunity: how does it relate to the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg 14:137-44
Liu, Z; Li, N; Neu, J (2005) Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr 94:386-93
Li, Nan; Liboni, Kellym; Fang, Mao Zhong et al. (2004) Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats. Am J Physiol Gastrointest Liver Physiol 286:G914-21
Liboni, Kellym; Li, Nan; Neu, Josef (2004) Mechanism of glutamine-mediated amelioration of lipopolysaccharide-induced IL-8 production in Caco-2 cells. Cytokine 26:57-65
Beierle, Elizabeth A; Chen, Mike K; Hartwich, Joseph E et al. (2004) Artificial rearing of mouse pups: development of a mouse pup in a cup model. Pediatr Res 56:250-5
Li, Nan; Lewis, Patricia; Samuelson, Don et al. (2004) Glutamine regulates Caco-2 cell tight junction proteins. Am J Physiol Gastrointest Liver Physiol 287:G726-33

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