GLP2R

GLP2R Full Name

glucagon-like peptide 2 receptor

GLP2R Introduction

GLP2R encodes the glucagon-like peptide 2 receptor, a G protein-coupled receptor (GPCR) that binds glucagon-like peptide-2 (GLP-2) to regulate intestinal growth, barrier function, and nutrient absorption. The receptor is primarily expressed in the gastrointestinal tract, particularly in the mucosa of the small and large intestine, where its activation by GLP-2 stimulates crypt cell proliferation, inhibits apoptosis, and enhances nutrient uptake. Upon ligand binding, GLP2R activates Gαs proteins to increase intracellular cAMP levels, which in turn activates PKA and EPAC signaling pathways to promote cell survival and proliferation. The receptor's expression is restricted mainly to enteroendocrine cells and subepithelial fibroblasts, from which paracrine signals are released to stimulate neighboring intestinal epithelial cells. This localized action makes GLP2R signaling an attractive target for treating intestinal disorders without systemic side effects.

Figure 1. Mechanisms of GLP-2 regulation of intestinal lipid handling. (Source: Mukherjee K, et al. 2024)

The therapeutic potential of GLP2R activation has been demonstrated in multiple clinical contexts. Teduglutide, a synthetic analog of GLP-2, has been approved for the treatment of short bowel syndrome (SBS), a condition characterized by malabsorption due to reduced functional intestinal surface area. In patients with SBS, teduglutide treatment reduces the need for parenteral nutrition by promoting intestinal adaptation and enhancing barrier function. Additionally, GLP2R signaling has shown promise in treating inflammatory bowel disease (IBD), where it reduces inflammation and promotes mucosal healing. Studies have also implicated GLP2R in the regulation of food intake and energy balance, suggesting broader metabolic roles beyond the intestine. The receptor's restricted expression pattern and well-characterized signaling mechanisms make it a safe and effective target for treating a range of gastrointestinal disorders.

Alternate Names for GLP2R

GLP2R; glucagon-like peptide 2 receptor; GLP-2R; GLP-2-R; GLP-2 receptor;

• 1. Mukherjee K, et al. GLP-2 regulation of intestinal lipid handling. Front Physiol. 2024 Feb 14;15:1358625.
  2. Sabra HK, et al. Efficacy and safety of glucagon-like peptide 2 in patients with short bowel syndrome: a systematic review and network meta-analysis. J Gastrointest Surg. 2024 Jul;28(7):1194-1205.