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

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

Author information

1
INSERM U995, Lille, France; Université Lille Nord de France, Lille, France; Intestinal Biotech Development, Lille, France;
2
INSERM U995, Lille, France; Université Lille Nord de France, Lille, France;
3
INSERM 913, CHU Hôtel Dieu, Nantes, France;
4
CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France;
5
INSERM U995, Lille, France; Intestinal Biotech Development, Lille, France;
6
Université Paris-Sud, Laboratoire "Cytokines, Chimiokines et Immunopathologie," Unité Mixte de Recherche S996, Clamart, France; INSERM, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Clamart, France; Service d'Anatomie et de Cytologie Pathologique, Unité Propre de Recherche de l'Enseignement Supérieur Associé 1320, Hôpital Robert Debré, France; Université Denis Diderot, Université Paris 7, Paris, France; and.
7
Université Lille Nord de France, Lille, France; EA 2693, Lille, France.
8
INSERM U995, Lille, France; Université Lille Nord de France, Lille, France; CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France;
9
INSERM U995, Lille, France; Université Lille Nord de France, Lille, France; CHU Lille, Service des maladies de l'appareil digestif et de la nutrition, Hôpital Claude Huriez, Lille, France; pdesreumaux@hotmail.com.

Abstract

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

PMID:
24875097
DOI:
10.1152/ajpgi.00389.2012
[Indexed for MEDLINE]
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