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

We wished to determine whether exogenous glucagon-like peptide (GLP)-2 infu sion stimulates intestinal growth in parenterally fed immature pigs. Piglet s (106-108 days gestation) were given parenteral nutrient infusion (TPN), T PN + human GLP-2 (25 nmol.kg(-1).day(-1)), or sow's milk enterally (ENT) fo r 6 days. Intestinal protein synthesis was then measured in vivo after a bo lus dose of [1-C-13] phenylalanine, and degradation was calculated from the difference between protein accretion and synthesis. Crypt cell proliferati on and apoptosis were measured in situ by 5-bromodeoxyuridine (BrdU) and te rminal 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 fraction al protein degradation rate, whereas ENT increased fractional protein synth esis 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 int estinal growth in premature, TPN-fed pigs by decreasing proteolysis and apo ptosis, whereas enteral nutrition acts via increased protein synthesis and cell proliferation and decreased apoptosis.