Examination of Expression and Function of TCF Genes in the Pancreatic Islets

Specific SNPs in intronic regions of the human TCF7L2 gene are associated with an elevated risk of T2D development and progression. Several investigations have suggested a role of TCF7L2 in pancreatic β-cells. Whether this transcription factor is indeed expressed in the pancreatic islets of rodent species, however, has been a controversial issue. Here, we found that TCF7L2 mRNA level was significantly lower in the pancreas compared to the gut or Ins-1 cell line. In addition, TCF7L2 mRNA abundance in the pancreas was decreased by insulin. Finally, both TCF7 and TCF7L1 but not LEF-1 could be detected in the mouse pancreas. mRNA abundance for these two transcription factors was also decreased by insulin, and the level of TCF7, TCF7L1, and TCF7L2 mRNAs could be down-regulated by HFD. We speculate that reduced expression of these TCF genes during hyperinsulinemia may alter the Wnt signalling pathway and therefore impair the function of β-cells.MAS