Intestinal growth-promoting properties of glucagon-like peptide-2 in mice.
Glucagon-like peptide-2 (GLP-2) has been shown to promote intestinal epithelial proliferation. We studied crypt cell proliferation, enterocyte cell death, and feeding behavior in GLP-2-treated mice. GLP-2 had no effect on food consumption [7.7 +/- 0.3 vs. 8.0 +/- 0.4 g/day, saline (control) vs. GLP-2-treated mice, P = not significant]; however, GLP-2 increased the crypt cell proliferation rate (46.0 +/- 1 vs. 57 +/- 5%, control vs. GLP-2, P < 0.01) and decreased the enterocyte apoptotic rate (5.9 +/- 0.7 vs. 2.8 +/- 0.2% apoptotic cells, control vs. GLP-2, P < 0.05) in small bowel (SB) epithelium. GLP-2 induced a significant increase in SB weight (1.3- to 1.75-fold increase over control, P < 0.05 to P < 0.001) in mice 1-24 mo of age. Increased SB weight was maintained after daily administration of GLP-2 to mice for 12 wk, and cessation of GLP-2 administration in older mice led to regression of (increased) SB weight and mucosal height. These observations suggest that GLP-2 regulates both cell proliferation and apoptosis and promotes intestinal growth after both short- and long-term administration in vivo.
Tsai
C H
CH
Department of Medicine, Banting and Best Diabetes Centre, Toronto Hospital, University of Toronto, Ontario, Canada.
Hill
M
M
Asa
S L
SL
Brubaker
P L
PL
Drucker
D J
DJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D015415:Biomarkers; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000254:growth & development; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D007082:Ileum / Q000254:growth & development; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D007583:Jejunum / Q000254:growth & development; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012727:Sex Characteristics; D013997:Time Factors
D015415:Biomarkers; D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D004763:Glucagon-Like Peptides