title: The therapeutic potential of targeting the glucagon-like peptide-2 receptor in gastrointestinal disease.
abstract: BACKGROUND
  Glucagon-like peptide-2 (GLP-2) is a pleiotropic intestinotrophic hormone that enhances digestive and absorptive capacity by acting through a limited population of intestinal GLP-2 receptors. The development of protease-resistant analogs or GLP-2/IgG fusion proteins confers a longer circulating half life than the native peptide. GLP-2 has garnered interest as a therapeutic most notably by reducing reliance on total parenteral nutrition in patients with short bowel syndrome.
  
  
  METHODS
  The clinical evidence for benefit in conditions requiring longer term treatment with GLP-2 receptor agonists, for example short bowel syndrome and inflammatory bowel disease. Benefits of short-term GLP-2 treatment are emerging in pre-clinical models, such as post-operative ileus, GI mucositis and conditions of altered intestinal permeability. The therapeutic utility of GLP-2 receptor agonists is limited by concern that it predisposes patients to gastrointestinal cancers, or their re-occurrence in cancer patients. This affects the types of diseases treated and, possibly, the duration of dosing.
  
  
  CONCLUSIONS
  GLP-2 is therapeutically attractive in diseases to enhance absorptive capacity, restore mucosal health and reduce inflammation. Long-term surveillance studies with a marketed therapeutic agent are needed to weigh the benefits of GLP-2 treatment against the potential effects on co-morbidities and increased risk of intestinal carcinogenesis.
authors.affiliation: Johnson & Johnson Biotechnology CoE, Cell Biology and Assay Technologies, Radnor, PA 19087, USA. phornby@its.jnj.com
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hornby
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Moore
mesh_terms: D000818:Animals; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D053767:Glucagon-Like Peptide 2 / Q000502:physiology; D000067758:Glucagon-Like Peptide-2 Receptor; D006801:Humans; D045823:Ileus / Q000188:drug therapy; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D052016:Mucositis / Q000188:drug therapy; D018027:Receptors, Glucagon / Q000819:agonists* / Q000502:physiology; D012778:Short Bowel Syndrome / Q000188:drug therapy
chemical_list: D053767:Glucagon-Like Peptide 2; D000067758:Glucagon-Like Peptide-2 Receptor; D018027:Receptors, Glucagon