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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 279; no. 6; pp. G1249 - G1256
• Main Authors: Burrin, D G, Stoll, B, Jiang, R, Petersen, Y, Elnif, J, Buddington, R K, Schmidt, M, Holst, J J, Hartmann, B, Sangild, P T
• Format: Journal Article
• Language: English
• Published: United States 01.12.2000
• Subjects: Animals; Animals, Newborn; Apoptosis; Dietary Proteins - metabolism; Enteral Nutrition; Female; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Humans; In Situ Nick-End Labeling; Intestine, Large - drug effects; Intestine, Large - growth & development; Intestine, Large - metabolism; Intestines - drug effects; Intestines - growth & development; Intestines - metabolism; Male; Pancreas - drug effects; Pancreas - growth & development; Pancreas - metabolism; Parenteral Nutrition, Total; Peptides - blood; Peptides - pharmacology; Stomach - drug effects; Stomach - growth & development; Stomach - metabolism; Swine
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.2000.279.6.G1249

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.