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

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

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Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5G 1L7.


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.

[Indexed for MEDLINE]

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