This research is designed to advance understanding of changes in active amino acid transport by the enterocyte after massive small bowel resection. The role of hormones and specific nutrients as mediators of these-changes will also be examined. The hypotheses to be tested are: 1. Active amino acid transport by the enterocyte is altered during adaptation after massive bowel resection. 2. Specific hormones influence amino acid transport during this adaptation. 3. Specific nutrients, including amino acids and short chain fatty acids (SCFA) may be beneficial after resection by improving amino acid uptake. New Zealand rabbits undergo 70% jejunoileal resection or sham operation. One week, one month, and six months later, small bowel mucosa will be processed to brush border membrane vesicles. Uptake of glutamine (GLN), arginine, alanine, and leucine will be quantified using a rapid mixing/filtration technique. Changes in plasma levels of neurotensin (NT) epidermal growth factor (EGF), and growth hormone (GH) will be determined by radioimmunoassay. Infusions of NT, EGF, GH and the somatostatin analogue octreotide will assess hormonal influence on amino acid transport. Octreotide's effect will be further verified by immuno- neutralization with specific antisera to NT, EGF, and GH. Dietary manipulation includes the provision of isonitrogenous, isocaloric diets with protein as whole protein, oligopeptides or free amino acids. SCFA will be supplemented either as free sodium butyrate or pectin. Influence of parenteral GLN on amino acid transport from both the lumen and the splanchnic circulation will also be quantified. The eventual goal is to develop nutrient/hormone combinations that will improve adaptation. It is hoped that the knowledge gained will contribute to new therapeutic strategies for patients with short gut syndrome.
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