Biologic properties and therapeutic potential of glucagon-like peptide-2

Background: Glucagon-like peptide-2 (GLP-2), a 33 amino acid, proglucagon-d erived peptide with intestinotrophic activity, is secreted from enteroendoc rine cells in the small and large intestine. Methods: This review describes recent advances in our understanding of GLP-2 physiology from rodent exper iments in vivo. Results: GLP-2 administration induces mucosal epithelial pr oliferation 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 t o DPP-IV exhibit enhanced biologic activity in vivo. GLP-2-treated bowel re tains normal to enhanced functional absorptive capacity. Furthermore, GLP-2 infusion prevents total parenteral nutrition (TPN)-associated intestinal h ypoplasia, and enhances bowel adaptation and nutrient absorption in rats fo llowing small bowel resection. GLP-2 also reverses weight lass and improves histologic and biochemical parameters of disease activity in mice with exp erimental 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.