GLP-2 system

Glucagon-Like-Peptide-2 (GLP-2) is a 33 amino acid peptide derived from posttranslational processing of protoglucagon in intestinal L-cells. Endogenous GLP-2 is released into the circulation following nutrient ingestion. One of the first demonstrations of the biological actions of GLP-2 was stimulation of intestinal growth through increased proliferation and decreased apoptosis of mucosal epithelial cells following the administration of exogenous GLP-2 to mice. The growth effects were specific for the intestine as GLP-2 had no effect on the growth of other tissues.

The GLP-2 peptide acts at a distinct G-protein coupled receptor that has been cloned from a variety of species. GLP-2 receptor expression is most abundant in the small intestine, colon and stomach with an expression pattern that is highly localized to specific cell types including subepithelial myofibroblasts, enteroendocrine cells and enteric and nodose ganglia of vagal neurons. GLP-2 receptor expression is also reported in brain, lung and pancreas. The GLP-2 receptor is not expressed on intestinal epithelial cells; hence, the intestinotrophic effect of GLP-2 is thought to be mediated indirectly through growth factors including IGF, KGF and ErbB ligands that act in a paracrine fashion to elicit biological actions.

GLP-2 has pronounced biological actions on the intestine resulting in beneficial effects to promote healing and maintain intestinal epithelial integrity under a variety of conditions (Estall 2006). Hence, GLP-2 agonists have therapeutic potential to treat or modify gastrointestinal disorders. A number of studies in animal models have demonstrated beneficial effects of GLP-2 agonists to prevent chemotherapy-induced intestinal mucositis. Worldwide, millions of people are treated for cancer by means of chemotherapy and/or radiotherapy. Many of these patients experience side effects that may be attributed to intestinal mucositis. One indirect side effect caused by intestinal mucositis is bacteremia and infection due to gastrointestinal bacterial strains that have escaped to the blood stream due to translocation caused by defective mucosal barrier.