Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration

Am J Physiol Gastrointest Liver Physiol. 2014 Aug 1;307(3):G274-85. doi: 10.1152/ajpgi.00389.2012. Epub 2014 May 29.


The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.

Keywords: enteroendocrine cell; glucagon-like peptide; inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Caco-2 Cells
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / genetics
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism
  • Gastrointestinal Agents / pharmacology*
  • Gene Expression Regulation
  • Glucagon-Like Peptide 2 / pharmacology*
  • Glucagon-Like Peptide-2 Receptor
  • HT29 Cells
  • Hep G2 Cells
  • Hepatectomy
  • Humans
  • Jurkat Cells
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / surgery
  • Liver Regeneration / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Glucagon / agonists*
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Trinitrobenzenesulfonic Acid


  • Anti-Inflammatory Agents
  • Gastrointestinal Agents
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-2 Receptor
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, Glucagon
  • Recombinant Proteins
  • Trinitrobenzenesulfonic Acid
  • Dextran Sulfate