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Endocrinology, doi:10.1210/en.2007-1142
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Endocrinology Vol. 149, No. 5 2341-2351
Copyright © 2008 by The Endocrine Society

Cross Talk between the Insulin and Wnt Signaling Pathways: Evidence from Intestinal Endocrine L Cells

Fenghua Yi1, Jane Sun1, Gareth E. Lim, I. George Fantus, Patricia L. Brubaker and Tianru Jin

Division of Cell and Molecular Biology (F.Y., I.G.F., T.J.), Toronto General Research Institute, University Health Network; Departments of Medicine (I.G.F., P.L.B., T.J.), Physiology (G.E.L., I.G.F., P.L.B., T.J.), and Laboratory Medicine and Pathobiology (J.S., T.J.); and Banting and Best Diabetes Centre (I.G.F., T.J.), Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5G 1L7

Address all correspondence and requests for reprints to: Tianru Jin, Room 10-354, 10th Floor, Toronto Medical Discovery Tower, MaRS Centre, University Health Network, 101 College Street, Toronto, Ontario, Canada M5G 1L7. E-mail: tianru.jin{at}utoronto.ca.

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 β-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 β-catenin content in the intestinal L cells was increased by insulin. Finally, insulin enhanced the binding of TCF-4 and β-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 β-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.







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Copyright © 2008 by The Endocrine Society