Signaling mechanisms of glucagon-like peptide 2-induced intestinal epithelial cell proliferation

J Surg Res. 2000 May 1;90(1):13-8. doi: 10.1006/jsre.2000.5818.


Background: Glucagon-like peptide 2 (GLP-2) stimulates intestinal epithelial growth with high potency and specificity. However, the intracellular signaling pathways responsible for the growth-stimulatory action of GLP-2 are not clearly understood. Here we report possible signaling pathways mediating GLP-2's proliferative actions in the human intestinal epithelial cell line Caco-2.

Materials and methods: Caco-2 cells were subcultured under serum-deprived conditions in the presence or absence of GLP-2 (10 microM) and varying concentrations of inhibitors of three candidate kinases: genistein, a global tyrosine kinase inhibitor; LY294002, a phosphatidylinositide (PI) 3-kinase inhibitor; and PD 098059, a mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitor. Proliferation was assessed using [(3)H]thymidine incorporation. Relative abundance of the phosphorylated forms of two specific mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, was assessed by Western blotting.

Results: GLP-2-treated cells demonstrated a greater than 10-fold increase in proliferation. This response was inhibited by genistein, LY294002, and PD 098059 in a dose-dependent fashion. A significantly greater abundance of the phosphorylated forms of both ERK-1 and ERK-2 was present in cells within 5 min of treatment with GLP-2.

Conclusions: GLP-2 stimulates the proliferation of Caco-2 cells in vitro. This increase in Caco-2 proliferation in response to GLP-2 may be due, at least in part, to the involvement of both the PI 3-kinase and the MAPK pathways.

MeSH terms

  • Caco-2 Cells
  • Cell Division / drug effects
  • DNA / biosynthesis
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptides
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Mitogen-Activated Protein Kinase 1 / physiology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / physiology
  • Peptides / pharmacology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Signal Transduction*


  • Glucagon-Like Peptide 2
  • Peptides
  • Glucagon-Like Peptides
  • DNA
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases