Biologic properties and therapeutic potential of glucagon-like peptide-2.
BACKGROUND
Glucagon-like peptide-2 (GLP-2), a 33 amino acid, proglucagon-derived peptide with intestinotrophic activity, is secreted from enteroendocrine cells in the small and large intestine.


METHODS
This review describes recent advances in our understanding of GLP-2 physiology from rodent experiments in vivo.


RESULTS
GLP-2 administration induces mucosal epithelial proliferation in small and large bowel and stomach. GLP-2 is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP-IV) to produce the biologically inactive form GLP-2(3-33), however, GLP-2 analogs that confer resistance to DPP-IV exhibit enhanced biologic activity in vivo. GLP-2-treated bowel retains normal to enhanced functional absorptive capacity. Furthermore, GLP-2 infusion prevents total parenteral nutrition (TPN)-associated intestinal hypoplasia, and enhances bowel adaptation and nutrient absorption in rats following small bowel resection. GLP-2 also reverses weight loss and improves histologic and biochemical parameters of disease activity in mice with experimental colitis.


CONCLUSIONS
GLP-2 is an intestine-derived peptide with intestinotrophic properties that may be therapeutically useful in diseases characterized by intestinal damage or insufficiency.
Drucker
D J
DJ
Department of Medicine, Banting and Best Diabetes Centre, The Toronto Hospital, University of Toronto, Canada.
Boushey
R P
RP
Wang
F
F
Hill
M E
ME
Brubaker
P L
PL
Yusta
B
B
D000818:Animals; D003092:Colitis / Q000188:drug therapy*; D004064:Digestive System / Q000187:drug effects*; D004068:Digestive System Physiological Phenomena; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010455:Peptides / Q000502:physiology* / Q000627:therapeutic use*; D051381:Rats
D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides