H. Nepomuceno1, A. Thomas1, P. Emengo1, R. Gonzalez2, G.L. Fell1, F.S. Jazi1, T. Rafeeqi1, J.C. Dunn1 1Stanford University, Department Of Surgery, Palo Alto, CA, USA 2Stanford University, Department Of Pediatrics, Palo Alto, CA, USA
Introduction: Mechanical lengthening has been demonstrated as a method to induce enterogenesis in porcine intestine. Although mechano-transductive cell signaling pathways underlying mechanical enterogenesis have been partially described, paracrine and endocrine mechanisms of signaling have not been previously explored. We hypothesized that biomechanical pathways activated during mechanical enterogenesis may lead to increased concentrations of circulating intestinal growth factor glucagon-like peptide 2.
Methods: Juvenile mini-Yucatan pigs underwent mechanical lengthening via spring insertion into the intestinal lumen. Serum samples were obtained pre- and post-mechanical lengthening and analyzed by enzyme-linked immunosorbent assay for GLP-2 levels. Data were evaluated for change in concentration based on differences in the location of mechanical lengthening, i.e. jejunal or ileal. Statistical analysis was performed with t-test; p<0.05 was considered significant.
Results: Serum samples from 38 mini-Yucatan pigs pre- and post-mechanical lengthening were analyzed for GLP-2 levels. 10 pigs had springs implanted in the ileum and 28 pigs had springs implanted in the jejunum. GLP-2 serum levels increased significantly following ileal lengthening (ileum p=0.043, jejunum p=0.37, all pigs p=0.082, Figure 1). Ileal lengthening led to a greater increase in serum GLP-2 levels than jejunal lengthening (p<0.01).
Conclusion: Glucagon-like peptide 2 is a hormone with trophic actions in the gastrointestinal tract, stimulating crypt cell proliferation and enhancement of nutrient absorption. GLP-2 is secreted by enteroendocrine L cells of the intestinal epithelium, with the highest abundance of L cells in the terminal ileum and colon. The observation of increased serum GLP-2 levels in ileal lengthening versus jejunal lengthening supports an endocrine-mediated effect of mechanical enterogenesis and suggests there may be systemic effects of lengthening that depend on the location of the lengthened intestinal segment.