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 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-(13)C]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.
Burrin
D G
DG
United States Department of Agriculture, Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Stoll
B
B
Jiang
R
R
Petersen
Y
Y
Elnif
J
J
Buddington
R K
RK
Schmidt
M
M
Holst
J J
JJ
Hartmann
B
B
Sangild
P T
PT
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D004044:Dietary Proteins / Q000378:metabolism*; D004750:Enteral Nutrition; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000378:metabolism; D007420:Intestine, Large / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000254:growth & development*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010289:Parenteral Nutrition, Total; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects / Q000254:growth & development; D013552:Swine
D004044:Dietary Proteins; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides