GLP-2 receptors in human disease: high expression in gastrointestinal stromal tumors and Crohn's disease

Mol Cell Endocrinol. 2012 Nov 25;364(1-2):46-53. doi: 10.1016/j.mce.2012.08.008. Epub 2012 Aug 19.

Abstract

Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoradiography
  • Crohn Disease / genetics*
  • Crohn Disease / metabolism
  • Crohn Disease / pathology
  • Female
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / metabolism
  • Gastrointestinal Stromal Tumors / pathology
  • Gene Expression*
  • Glucagon-Like Peptide 2 / metabolism*
  • Glucagon-Like Peptide-2 Receptor
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestines / pathology
  • Middle Aged
  • Myenteric Plexus / metabolism
  • Myenteric Plexus / pathology
  • Receptors, Glucagon / genetics*
  • Receptors, Glucagon / metabolism
  • Up-Regulation

Substances

  • GLP2R protein, human
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-2 Receptor
  • Receptors, Glucagon