Glucagon-like peptide-2 enhances intestinal epithelial barrier function ofboth transcellular and paracellular pathways in the mouse

Background and aims-Glucagon-like peptide-2 (GLP-2) is a recently identifie d potent intestinotrophic factor. We have evaluated the effect of GLP-2 tre atment on intestinal epithelial barrier function in mice. Methods-CD-1 mice were injected subcutaneously with GLP-2 or a protease res istant analogue, h[Gly(2)]GLP-2, twice daily for up to 10 days. Saline inje cted mice served as controls. Jejunal segments were mounted in Ussing chamb ers. Tissue conductance was measured and unidirectional fluxes were determi ned for (i) Na+ and the small inert probe Cr-EDTA (both transported via the paracellular pathway) and (ii) the macromolecule horseradish peroxidase (H RP, transported via the transcellular pathway). Results-Mice treated with GLP-2 or h[Gly(2)]GLP-2 for 10 days demonstrated significantly reduced intestinal conductance and fluxes of Na+, Cr-EDTA, an d HRP. Electron microscopy confirmed that GLP-2 reduced endocytic uptake of HRP into enterocytes. Functional changes (evident by four hours) preceded morphological changes (evident by 38 hours). Conclusions-GLP-2 enhances intestinal epithelial barrier function by affect ing both paracellular and transcellular pathways and thus may be of therape utic value in a number of gastrointestinal conditions.