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 expressed in the intestinal enteroendocrine L-cell. The primary stimulus for GLP-2 secretion is nutrient intake, and involves direct luminal stimulation of the L-cell as well as indirect enteroendocrine and neural mechanisms. The biological activity of GLP-2 in circulation is regulated by the proteolytic cleavage of the N-terminus by dipeptidylpeptidase IV. Several studies have shown that GLP-2 has specific trophic effects on the small and large intestine, which are mediated by stimulation of cell proliferation and inhibition of apoptosis and proteolysis. GLP-2 also has been shown to suppress gastric motility and acid secretion, increase hexose transport activity and suppress food intake, specifically when infused centrally. The actions of GLP-2 are mediated by a G-protein-linked, membrane receptor (GLP-2R) that is localized largely to the gastrointestinal tract, but also is found in the brain. 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 responsive to the trophic effect of GLP-2 until after birth. Based on its efficacy in preventing atrophy and stimulating growth in the neonatal gut, GLP-2 may be a promising therapeutic adjuvant for treatment of infants with compromised gut function.