Glucagon-Like Peptide-2 (GLP-2)
A 33 amino acid hormone co-secreted with GLP-1 from intestinal L-cells that promotes growth and function of the intestinal mucosa. Teduglutide is a GLP-2 analogue approved for short bowel syndrome, where it stimulates intestinal adaptation and reduces the need for parenteral nutrition.
Technical Context
GLP-2 (33 aa) is co-secreted with GLP-1 from L-cells and acts on the GLP-2 receptor (a class B GPCR) expressed on enteric neurons, subepithelial myofibroblasts, and intestinal endocrine cells (not directly on enterocytes). GLP-2R activation stimulates intestinal crypt cell proliferation, inhibits enterocyte apoptosis, increases villus height and crypt depth, enhances intestinal blood flow, and upregulates nutrient transporter expression. Native GLP-2 has a half-life of approximately 7 minutes (also a DPP-4 substrate). Teduglutide (Gattex/Revestive) has an Ala2→Gly substitution conferring DPP-4 resistance, extending its half-life to approximately 2-3 hours, enabling once-daily SC injection. Clinical trials showed significant reduction in parenteral nutrition requirements in short bowel syndrome patients.