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Am J Physiol Gastrointest Liver Physiol 279: G1249-G1256, 2000;
0193-1857/00 $5.00
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Vol. 279, Issue 6, G1249-G1256, December 2000

GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis

D. G. Burrin1, B. Stoll1, R. Jiang1, Y. Petersen2, J. Elnif2, R. K. Buddington3, M. Schmidt2, J. J. Holst4, B. Hartmann4, and P. T. Sangild2

1 United States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030; 2 Departments of Animal Science and Health, Royal Veterinary and Agricultural University, DK-1870 Copenhagen, Denmark; 3 Department of Biological Sciences, Mississippi State University, Mississippi State, Mississippi 39762; and 4 Department of Medical Physiology, University of Copenhagen, DK-2200 Copenhagen, Denmark

We wished to determine whether exogenous glucagon-like peptide (GLP)-2 infusion stimulates intestinal growth in parenterally fed immature pigs. Piglets (106-108 days gestation) were given parenteral nutrient infusion (TPN), TPN + human GLP-2 (25 nmol · kg-1 · day-1), or sow's milk enterally (ENT) for 6 days. Intestinal protein synthesis was then measured in vivo after a bolus dose of [1-13C]phenylalanine, and degradation was calculated from the difference between protein accretion and synthesis. Crypt cell proliferation and apoptosis were measured in situ by 5-bromodeoxyuridine (BrdU) and terminal dUTP nick-end labeling (TUNEL), respectively. Intestinal protein and DNA accretion rates and villus heights were similar in GLP-2 and ENT pigs, and both were higher (P < 0.05) than in TPN pigs. GLP-2 decreased fractional protein degradation rate, whereas ENT increased fractional protein synthesis rate compared with TPN pigs. Percentage of TUNEL-positive cells in GLP-2 and ENT groups was 48 and 64% lower, respectively, than in TPN group (P < 0.05). However, ENT, but not GLP-2, increased percentage of BrdU-positive crypt cells above that in TPN piglets. We conclude that GLP-2 increases intestinal growth in premature, TPN-fed pigs by decreasing proteolysis and apoptosis, whereas enteral nutrition acts via increased protein synthesis and cell proliferation and decreased apoptosis.

protein synthesis; protein degradation; total parenteral nutrition; preterm infants


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