Induction of intestinal epithelial proliferation by glucagon-like peptide 2.
Injury, inflammation, or resection of the small intestine results in severe compromise of intestinal function. Nevertheless, therapeutic strategies for enhancing growth and repair of the intestinal mucosal epithelium are currently not available. We demonstrate that nude mice bearing subcutaneous proglucagon-producing tumors exhibit marked proliferation of the small intestinal epithelium. The factor responsible for inducing intestinal proliferation was identified as glucagon-like peptide 2 (GLP-2), a 33-aa peptide with no previously ascribed biological function. GLP-2 stimulated crypt cell proliferation and consistently induced a marked increase in bowel weight and villus growth of the jejunum and ileum that was evident within 4 days after initiation of GLP-2 administration. These observations define a novel biological role for GLP-2 as an intestinal-derived peptide stimulator of small bowel epithelial proliferation.
Drucker
D J
DJ
Department of Medicine, The Toronto Hospital and Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Erlich
P
P
Asa
S L
SL
Brubaker
P L
PL
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D053771:Glicentin; D005934:Glucagon / Q000096:biosynthesis* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D005935:Glucagonoma / Q000378:metabolism / Q000473:pathology*; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D007583:Jejunum / Q000187:drug effects / Q000473:pathology; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D010187:Pancreatic Hormones / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D052336:Proglucagon; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011498:Protein Precursors / Q000096:biosynthesis* / Q000494:pharmacology; D051381:Rats; D014183:Transplantation, Heterologous
D053767:Glucagon-Like Peptide 2; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D010455:Peptides; D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D052336:Proglucagon; D004763:Glucagon-Like Peptides; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon