TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells.
| Title: | TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells. |
|---|---|
| Authors: | Loder MK; Imperial College, Faculty of Medicine, Department of Cell Biology, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, UK. m.loder@imperial.ac.uk; da Silva Xavier G; McDonald A; Rutter GA |
| Source: | Biochemical Society transactions [Biochem Soc Trans] 2008 Jun; Vol. 36 (Pt 3), pp. 357-9. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Portland Press On The Behalf Of The Biochemical Society Country of Publication: England NLM ID: 7506897 Publication Model: Print Cited Medium: Print ISSN: 0300-5127 (Print) Linking ISSN: 03005127 NLM ISO Abbreviation: Biochem Soc Trans Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Portland Press On The Behalf Of The Biochemical Society |
| MeSH Terms: | Gene Expression Regulation*; Insulin/*genetics ; Insulin/*metabolism ; Insulin-Secreting Cells/*cytology ; Insulin-Secreting Cells/*metabolism ; TCF Transcription Factors/*metabolism; Diabetes Mellitus/genetics ; TCF Transcription Factors/genetics ; Transcription Factors/metabolism ; beta Catenin/metabolism ; Animals ; Insulin Secretion ; Mice ; Transcription Factor 7-Like 2 Protein |
| 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. |
| Grant Information: | 13/0004672 United Kingdom DUK_ Diabetes UK; 067081/z/02/z United Kingdom WT_ Wellcome Trust; 081958/z/07/z United Kingdom WT_ Wellcome Trust |
| Substance Nomenclature: | 0 (Insulin); 0 (TCF Transcription Factors); 0 (TCF7L2 protein, human); 0 (Tcf7l2 protein, mouse); 0 (Transcription Factor 7-Like 2 Protein); 0 (Transcription Factors); 0 (beta Catenin) |
| Entry Date(s): | Date Created: 20080517 Date Completed: 20081103 Latest Revision: 20250529 |
| Update Code: | 20260130 |
| DOI: | 10.1042/BST0360357 |
| PMID: | 18481957 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't