Cross talk between the insulin and Wnt signaling pathways: evidence from intestinal endocrine L cells

Endocrinology. 2008 May;149(5):2341-51. doi: 10.1210/en.2007-1142. Epub 2008 Feb 7.


The proglucagon gene (glu) encodes the incretin hormone glucagon-like peptide-1 (GLP-1), produced in the intestinal endocrine L cells. We found previously that the bipartite transcription factor beta-catenin/T cell factor (cat/TCF), the major effector of the canonical Wnt signaling pathway, activates intestinal glu expression and GLP-1 production. We show here that 100 nm insulin stimulated glu expression and enhanced GLP-1 content in the intestinal GLUTag L cell line as well as in primary fetal rat intestinal cell cultures. Increased intestinal glu mRNA expression and GLP-1 content were also observed in vivo in hyperinsulinemic MKR mice. In the GLUTag cells, insulin-induced activation of glu expression occurred through the same TCF site that mediates cat/TCF activation. Phosphatidylinositol 3-kinase inhibition, but not protein kinase B inhibition, attenuated the stimulation by insulin. Furthermore, nuclear beta-catenin content in the intestinal L cells was increased by insulin. Finally, insulin enhanced the binding of TCF-4 and beta-catenin to the TCF site in the glu promoter G2 enhancer element, as determined by quantitative chromatin immunoprecipitation assay. Collectively, these findings indicate that enhancement of beta-catenin nuclear translocation and cat/TCF binding are among the mechanisms underlying cross talk between the insulin and Wnt signaling pathways in intestinal endocrine L cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Cricetinae
  • Enhancer Elements, Genetic
  • Enteroendocrine Cells / drug effects*
  • Enteroendocrine Cells / metabolism
  • Enteroendocrine Cells / physiology
  • Female
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Mice
  • Pregnancy
  • Proglucagon / genetics
  • Proglucagon / metabolism
  • Protein Binding / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor Cross-Talk / drug effects*
  • Receptor Cross-Talk / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • TCF Transcription Factors / metabolism
  • Wnt Proteins / metabolism
  • Wnt Proteins / physiology*
  • beta Catenin / metabolism


  • Insulin
  • RNA, Messenger
  • TCF Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • Proglucagon