Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon-like peptide 2.
The control of intestinal epithelial growth is regulated by interactions of growth factors in various cellular compartments of the small and large bowel. Little information is available on the intestinal growth response to combinations of growth factors. We studied the intestinotrophic properties of a dipeptidyl peptidase IV resistant glucagon-like peptide 2 (GLP-2) analog, human [Gly2]GLP-2 (h[Gly2]GLP-2), as well as of epidermal growth factor (EGF), long [Arg3]insulin-like growth factor I (LR3IGF-I), [Gly1]IGF-II, and human growth hormone (hGH), administered by subcutaneous injection alone or in combination in mice. At the doses tested, h[Gly2]GLP-2 was the most potent agent for increasing small and large bowel mass. Mice treated with h[Gly2]GLP-2 and either GH or IGF-I exhibited greater increases in histological parameters of small intestinal growth than did mice treated with h[Gly2]GLP-2 alone. Administration of all five growth factors together induced significant increases in crypt plus villus height and in small and large bowel length and weight. The results of these experiments define regional differences in both the cellular targets and relative activities of intestinotrophic molecules and raise the possibility that selective growth factor combinations may be useful for enhancement of intestinal adaptation in vivo.
Drucker
D J
DJ
Department of Medicine, Banting and Best Diabetes Centre, Toronto Hospital, University of Toronto, Ontario, Canada.
DeForest
L
L
Brubaker
P L
PL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006133:Growth Substances / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007082:Ileum; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000031:analogs & derivatives / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects; D007420:Intestine, Large / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats
D053767:Glucagon-Like Peptide 2; D006133:Growth Substances; C084339:LR(3)IGF-I; D010455:Peptides; D019382:Human Growth Hormone; D004815:Epidermal Growth Factor; D004763:Glucagon-Like Peptides; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II