TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells

Merewyn K Loder, Gabriela da Silva Xavier, Angela McDonald, Guy A Rutter

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

Abstract

Genetic studies have linked the risk of Type 2 diabetes with SNPs (single nucleotide polymorphisms) in the gene encoding the Wnt signalling-associated transcription factor, TCF7L2 (T-cell factor 7-like 2). The risk alleles have been associated with reduced glucose and GLP-1 (glucagon-like peptide 1)-stimulated insulin secretion. Recent evidence has suggested that inheritance of the at-risk T allele at SNP rs7903146 may increase the expression of TCF7L2 in adult human islets. However, the cellular mechanisms by which changes in TCF7L2 levels may affect insulin secretion are unclear. In the present paper, we describe the use of RNA silencing to investigate the role of TCF7L2 on insulin secretion and gene expression in rodent islets. We find that reduced TCF7L2 expression reduces glucose-simulated insulin secretion and insulin gene expression while slightly potentiating glucose stimulated changes in intracellular free Ca(2+) concentrations.

Original languageEnglish
Pages (from-to)357-9
Number of pages3
JournalBiochemical Society Transactions
Volume36
Issue numberPt 3
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Animals
  • Diabetes Mellitus/genetics
  • Gene Expression Regulation
  • Insulin/genetics
  • Insulin-Secreting Cells/cytology
  • Mice
  • TCF Transcription Factors/genetics
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors/metabolism
  • beta Catenin/metabolism

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