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 Ca2+ concentrations.
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June 2008
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Conference Article|
May 21 2008
TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic β-cells
Merewyn K. Loder;
1Imperial College, Faculty of Medicine, Department of Cell Biology, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, U.K.
2To whom correspondence should be addressed (email m.loder@imperial.ac.uk).
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Gabriela da Silva Xavier;
Gabriela da Silva Xavier
1
1Imperial College, Faculty of Medicine, Department of Cell Biology, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, U.K.
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Angela McDonald;
Angela McDonald
1Imperial College, Faculty of Medicine, Department of Cell Biology, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, U.K.
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Guy A. Rutter
Guy A. Rutter
1Imperial College, Faculty of Medicine, Department of Cell Biology, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, U.K.
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Biochem Soc Trans (2008) 36 (3): 357–359.
Article history
Received:
December 18 2007
Citation
Merewyn K. Loder, Gabriela da Silva Xavier, Angela McDonald, Guy A. Rutter; TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic β-cells. Biochem Soc Trans 1 June 2008; 36 (3): 357–359. doi: https://doi.org/10.1042/BST0360357
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