Glucagon-like peptide 2: A nutrient-responsive gut growth factor

Glucagon-like peptide 2 (GLP-2) is a 33-amino acid peptide derived from the tissue-specific, post-translational processing of the proglucagon gene exp ressed in the intestinal enteroendocrine L-cell. The primary stimulus for G LP-2 secretion is nutrient intake, and involves direct luminal stimulation of the L-cell as well as indirect enteroendocrine and neural mechanisms. Th e biological activity of GLP-2 in circulation is regulated by the proteolyt ic cleavage of the N-terminus by dipeptidylpeptidase IV. Several studies ha ve shown that GLP-2 has specific trophic effects on the small and large int estine, which are mediated by stimulation of cell proliferation and inhibit ion of apoptosis and proteolysis. GLP-2 also has been shown to suppress gas tric motility and acid secretion, increase hexose transport activity and su ppress food intake, specifically when infused centrally. The actions of GLP -2 are mediated by a G-protein-linked, membrane receptor (GLP-2R) that is l ocalized largely to the gastrointestinal tract, but also is found in the br ain. The secretion of GLP-2 and expression of the GLP-2R are present in the late gestation fetus. However, the developing intestine does not become re sponsive to the trophic effect of GLP-2 until after birth. Based on its eff icacy in preventing atrophy and stimulating growth in the neonatal gut, GLP -2 may be a promising therapeutic adjuvant for treatment of infants with co mpromised gut function.