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 pro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-07, Vol.93 (15), p.7911-7916
Main Authors: Drucker, Daniel J., Ehrlich, Peter, Asa, Sylvia L., Brubaker, Patricia L.
Format: Article
Language:English
Subjects:
Animals
Cell Division - drug effects
Cell growth
Crypts
Epithelial cells
Glicentin
Glucagon - biosynthesis
Glucagon - pharmacology
Glucagon-Like Peptide 1
Glucagon-Like Peptide 2
Glucagon-Like Peptides
Glucagonoma - metabolism
Glucagonoma - pathology
Histology
Ileum
Ileum - drug effects
Ileum - pathology
Immunohistochemistry
Intestinal Mucosa - drug effects
Intestinal Mucosa - pathology
Jejunum
Jejunum - drug effects
Jejunum - pathology
Kinetics
L cells
Medical research
Mice
Mice, Nude
Organ Size - drug effects
Pancreatic Hormones - pharmacology
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Peptide Fragments - pharmacology
Peptides
Peptides - pharmacology
Proglucagon
Proliferating Cell Nuclear Antigen - analysis
Protein Precursors - biosynthesis
Protein Precursors - pharmacology
Rats
Rodents
Small intestine
Transplantation, Heterologous
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.15.7911