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Diabetologia
Published in: Diabetologia 10/2012

Open Access 01-10-2012 | Commentary

Impact of transcription factor 7-like 2 (TCF7L2) on pancreatic islet function and morphology in mice and men

Author: E. Renström

Published in: Diabetologia | Issue 10/2012

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Abstract

Common genetic variations in the gene encoding transcription factor 7-like 2 (TCF7L2) reveal the strongest association with type 2-diabetes known to date. These lead to impaired insulin production and output, but the mechanisms of disease remain incompletely known. In this issue of Diabetologia, two publications provide new insights into TCF7L2-dependent diabetes.
Literature
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Saxena R, Voight BF, Lyssenko V et al (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336PubMedCrossRef
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Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885PubMedCrossRef
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Zeggini E, McCarthy MI (2007) TCF7L2: the biggest story in diabetes genetics since HLA? Diabetologia 50:1–4PubMedCrossRef
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Zeggini E, Weedon MN, Lindgren CM et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341PubMedCrossRef
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Chang YC, Chang TJ, Jiang YD et al (2007) Association study of the genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the Chinese population. Diabetes 56:2631–2637PubMedCrossRef
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da Silva Xavier G, Mondragon A, Sun G, Chen L, McGinty JA, French PM, Rutter GA (2012) Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice. Diabetologia. doi:10.​1007/​s00125-012-2600-7
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da Silva XG, Loder MK, McDonald A et al (2009) TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes 58:894–905CrossRef
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Shu L, Matveyenko AV, Kerr-Conte J, Cho JH, McIntosh CH, Maedler K (2009) Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 18:2388–2399PubMedCrossRef
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Zhou Y, Zhang E, Berggreen C et al (2012) Survival of pancreatic beta cells is partly controlled by a TCF7L2-p53-p53INP1-dependent pathway. Hum Mol Genet 21:196–207PubMedCrossRef
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Lyssenko V, Lupi R, Marchetti P et al (2007) Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 117:2155–2163PubMedCrossRef
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Prokunina-Olsson L, Welch C, Hansson O et al (2009) Tissue-specific alternative splicing of TCF7L2. Hum Mol Genet 18:3795–3804PubMedCrossRef
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Villareal DT, Robertson H, Bell GI et al (2010) TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action. Diabetes 59:479–485PubMedCrossRef
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Liu Z, Habener JF (2008) Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem 283:8723–8735PubMedCrossRef
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O Le Bacquer JK-C, S Gargani, N Delalleau, M Huyvaert, V Gmyr, P Froguel, B Neve, F Pattou (2012) TCF7L2 rs7903146 impairs islet function and morphology of non-diabetic individuals. Diabetologia. doi:10.​1007/​s00125-012-2660-8
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Le Bacquer O, Shu L, Marchand M et al (2012) TCF7L2 splice variants have distinct effects on beta-cell turnover and function. Hum Mol Genet 20:1906–1915CrossRef
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Metadata
Title
Impact of transcription factor 7-like 2 (TCF7L2) on pancreatic islet function and morphology in mice and men
Author
E. Renström
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2659-1

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