Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators

Abstract

Dubé PE, Brubaker PL. Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators.

Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats

“…IGF-I and GLP-2 are nutrient-regulated hormones that mediate, in part, the intestinotrophic effects of EN (10,26,28). Moreover, the actions of IGF-I and GLP-2 may be interrelated, as evidence from IGF-I knockout mice suggest that IGF-I is an essential mediator of the intestinotrophic actions of GLP-2 (11).…”

“…GLP-2 is secreted primarily by the ileum in response to EN and is rapidly inactivated by DPP-IV cleavage and cleared by the kidney (10). Rats given ENϩGLP-2 showed a significant 28% increase in concentration of plasma GLP-2, a significant 102% increase in ileum proglucagon mRNA expression, no change in ileal DPP-IV specific activity, and a significant 75% decrease in plasma DPP-IV activity compared with GLP-2 alone.…”

“…GLP-2 is secreted in response to nutrient intake and is rapidly inactivated by dipeptidyl peptidase-IV (DPP-IV) with a biological half-life of ϳ7 min (10). Previous studies indicate that GLP-2 is a key mediator of intestinal adaptive growth through stimulation of epithelial cell proliferation and inhibition of apoptosis in a variety of models of intestinal dysfunction in mice, rats, and pigs (1,6,11).…”

“…Expression of the GLP-2 receptor (GLP-2R), a G protein-coupled receptor, occurs primarily in the gastrointestinal tract and central nervous system, with limited expression in lung, cervix, and vagal afferents (24,27). Within the intestine, the GLP-2R has been localized to enteroendocrine cells, enteric neurons, and subepithelial myofibroblasts (10,27). In contrast, the target cells for intestinal growth, crypt epithelial cells, and enterocytes do not express the GLP-2R.…”

“…In contrast, the target cells for intestinal growth, crypt epithelial cells, and enterocytes do not express the GLP-2R. This has led to the hypothesis that GLP-2 action requires downstream mediators to induce intestinal growth and regulate other aspects of intestinal physiology (10).…”