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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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