Glucagon-like peptide 2 receptor (GLP2R) (GLP2R)

The Glucagon-like peptide 2 receptor (GLP2R) is a Class B G protein-coupled receptor primarily expressed in the gastrointestinal tract, specifically on enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons [1, 3, 6]. It is the specific receptor for glucagon-like peptide-2 (GLP-2), a 33-amino acid peptide hormone co-secreted with GLP-1 from intestinal L-cells following nutrient ingestion [4, 11]. Activation of GLP2R initiates a cascade of signaling events, including the stimulation of adenylyl cyclase and the release of secondary mediators like IGF-1, which promote intestinal growth by increasing crypt cell proliferation and inhibiting enterocyte apoptosis [2, 9]. These trophic actions lead to increased villus height and expanded mucosal surface area, significantly enhancing the gut's capacity for nutrient and fluid absorption [2, 4]. In clinical medicine, GLP2R is a critical therapeutic target for managing Short Bowel Syndrome (SBS), a condition characterized by intestinal failure and a reliance on parenteral nutrition [2, 13]. Drugs such as teduglutide, a degradation-resistant GLP-2 analog, act as potent GLP2R agonists to facilitate intestinal adaptation and reduce the volume of parenteral support required by patients [13]. Beyond SBS, the receptor is being explored for its potential to treat other conditions involving mucosal injury, such as Crohn's disease and chemotherapy-induced mucositis, due to its ability to reinforce the intestinal barrier and modulate local blood flow [2, 7, 12]. However, therapeutic use of GLP2R agonists requires careful monitoring for potential safety concerns, most notably the risk of promoting the growth of pre-existing intestinal neoplasia due to the receptor's potent proliferative effects [9, 11].

Other names

GLP2RGLP-2 receptorGLP-2-RGlucagon-like peptide 2 receptor

The mechanism of action involves the activation of the GLP-2 receptor, a Class B G protein-coupled receptor, which stimulates adenylyl cyclase and increases intracellular cAMP levels [1, 2]. This signaling pathway triggers the release of downstream growth factors, such as insulin-like growth factor 1 (IGF-1) and keratinocyte growth factor (KGF), from subepithelial myofibroblasts and enteric neurons [9]. These mediators then act on the intestinal epithelium to stimulate crypt cell proliferation, inhibit enterocyte apoptosis, and enhance the expression of nutrient transporters, ultimately increasing the functional surface area and barrier integrity of the gut [2, 4, 7].