Glucagon-like peptide 2 increases efficacy of distraction enterogenesis

Background: Application of distractive forces to small bowel induces intestinal growth, or enterogenesis. This emerging area of research may provide treatment for short bowel syndrome. Glucagon-like peptide 2(GLP-2) has also been reported to induce small bowel growth after bowel resection. We hypothesized that exogenous GLP-2 will result in enhanced distraction-induced enterogenesis.

Methods: Distraction-induced model was performed in 10-wk-old C57BL/6 mice using osmotic forces with high molecular weight polyethylene glycol (PEG)-stretch. Four groups were studied: Control group (PEG-/GLP-2-); PEG-stretch (PEG+/GLP-2-); GLP-2 control (PEG-/GLP-2+); and GLP-2 stretch (PEG+/GLP-2+). GLP-2 was given via subcutaneous osmotic pump over the 5 d of experiment. Morphology was measured by histomicrography. Epithelial cell (EC) proliferation was measured with proliferating cell nuclear antigen immunofluorescent staining. Total intestinal growth and blood vessel volume was assessed with Micro computed tomography volumetry. Vascular endothelial growth factor, fibroblast growth factor 1 and 2, and platelet-derived growth factor were measured by reverse-transcriptase polymerase chain reaction.

Results: EC proliferation increased significantly in all groups compared with controls, but was greatest in the GLP-2 stretch group. Diameter and length significantly increased in the PEG-stretch and GLP-2 stretch groups. Moreover, there was statistically greater diameter, crypt depth and EC proliferation in the GLP-2 stretch versus PEG-stretch groups. GLP-2 stretch vessel volume was greater than all other groups and was significantly increased compared with controls. The relative expression of platelet-derived growth factor increased significantly in the PEG-stretch group versus the Control group.

Conclusions: GLP-2 had an additive effect on EC proliferation, tissue growth, histomorphology, and vascularization. We also demonstrated a unique action of GLP-2, the enhancement of intestinal vascularization. The combination of enterogenesis and GLP-2 may yield an improved approach to treat short bowel syndrome.