Glucagon-like peptide 2: an update

Abstract

Purpose of review Glucagon-like peptide 2 (GLP-2) is a 33-amino acid peptide secreted in a nutrient-dependent manner from gut enteroendocrine cells. The proliferative and antiapoptotic actions of GLP-2 lead to expansion of the mucosal surface area and enhanced capacity for nutrient absorption in multiple models of experimental intestinal injury. These findings have raised the possibility that GLP-2 administration may produce therapeutic benefit in humans with intestinal insufficiency. Recent findings The actions of GLP-2 appear restricted to the gastrointestinal tract, central nervous system, and skeleton. GLP-2 exerts its effects through a G-protein–coupled receptor expressed in enteric neurons or enteroendocrine cells, suggesting that many of its actions are likely indirect through as yet unidentified secondary mediators. Exogenous administration of GLP-2 to mice, rats, or pigs reduces morbidity associated with intestinal damage and improves the structure and function of the intestinal mucosa. GLP-2 also exerts anabolic actions in bone via prevention of resorption. GLP-2 may also act in the brain to enhance neuronal survival via direct antiapoptotic actions. The cytoprotective and proliferative actions of GLP-2 highlight the need for further information on the efficacy and safety of long-term administration of GLP-2 in human subjects. Summary The available evidence suggests that GLP-2 upregulates pathways promoting restoration of intestinal barrier and absorptive function, leading to reduced bacterial translocation, improved nutrient uptake, and enhanced energy absorption. Degradation-resistant GLP-2 analogues are currently being tested in human clinical trials of subjects with inflammatory bowel disease and short bowel syndrome. Hence, GLP-2 may ultimately be used as a therapeutic agent for the treatment of metabolic disorders characterized by insufficient nutrient absorption.