GLP-2

Glucagon-like peptide-2 stimulates intestinal epithelial proliferation and reduces apoptosis in multiple rodent models of gut injury^[1]

This foundational study characterized GLP-2's intestinotrophic effects across several rodent models including neonatal, chemotherapy-induced, and TPN (total parenteral nutrition)-induced intestinal atrophy. Daily subcutaneous GLP-2 produced 2- to 3-fold increases in small intestinal weight, crypt depth, and villus height compared to vehicle controls in all three models within seven days. Bromodeoxyuridine labeling confirmed that GLP-2 increased crypt epithelial cell proliferation rate, while TUNEL staining showed a 40-60% reduction in apoptotic enterocytes. The effect was mediated by the GLP-2 receptor, which was localized to subepithelial myofibroblasts, not enterocytes directly, placing GLP-2R-expressing cells upstream of the intestinal epithelial proliferative response.

Last verified: 2026-04-03

GLP-2 enhances gut barrier function by regulating tight junction protein expression via IGF-1-dependent signaling^[2]

This mechanistic study investigated how GLP-2 improves intestinal epithelial barrier integrity in mouse small intestinal injury models and in differentiated Caco-2 monolayers. GLP-2 increased claudin-3, occludin, and ZO-1 tight junction protein expression in the jejunum over 72 hours, as measured by immunofluorescence and Western blot. Using an IGF-1R blocking antibody, the authors demonstrated that GLP-2's tight junction effects were abrogated, linking barrier improvement to the GLP-2 to GLP-2R to IGF-1 paracrine signaling axis. These findings established a molecular mechanism for GLP-2's observed reduction in intestinal permeability in short bowel syndrome research models.

Last verified: 2026-04-03