The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus

Mol Endocrinol. 2008 Nov;22(11):2383-92. doi: 10.1210/me.2008-0135. Epub 2008 Jul 3.


Since the relationship between TCF7L2 (also known as TCF-4) polymorphisms and type 2 diabetes mellitus was identified in 2006, extensive genome-wide association examinations in different ethnic groups have further confirmed this relationship. As a component of the bipartite transcription factor beta-catenin/TCF, TCF7L2 is important in conveying Wnt signaling during embryonic development and in regulating gene expression during adulthood. Although we still do not know mechanistically how the polymorphisms within the intron regions of TCF7L2 affect the risk of type 2 diabetes, this transcriptional regulator was shown to be involved in stimulating the proliferation of pancreatic beta-cells and the production of the incretin hormone glucagon-like peptide-1 in intestinal endocrine L cells. In this review, we introduce background knowledge of TCF7L2 as a component of the Wnt signaling pathway, summarize recent findings demonstrating the association between TCF7L2 polymorphisms and the risk of type 2 diabetes, outline experimental evidence of the potential function of TCF7L2 in pancreatic and intestinal endocrine cells, and present our perspective views.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Enteroendocrine Cells / physiology
  • Humans
  • Insulin-Secreting Cells / physiology
  • Models, Biological
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Signal Transduction
  • TCF Transcription Factors / chemistry
  • TCF Transcription Factors / genetics*
  • TCF Transcription Factors / physiology*
  • Transcription Factor 7-Like 2 Protein
  • Wnt Proteins / genetics
  • Wnt Proteins / physiology


  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Wnt Proteins