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Diabetologia (2014) 57:785796 DOI 10.1007/s00125-013-3154-z
ARTICLE
Alternative human liver transcripts of TCF7L2 bindto the gluconeogenesis regulator HNF4 at the protein level
Bernadette Neve & Olivier Le Bacquer & Sandrine Caron & Marlne Huyvaert &
Audrey Leloire & Odile Poulain-Godefroy & Ccile Lecoeur & Franois Pattou &
Bart Staels & Philippe Froguel
Received: 3 July 2013 /Accepted: 10 December 2013 /Published online: 26 January 2014 # Springer-Verlag Berlin Heidelberg 2014
AbstractAims/hypothesis Gene polymorphisms of TCF7L2 are associated with increased risk of type 2 diabetes and transcription factor 7-like 2 (TCF7L2) plays a role in hepatic glucose metabolism. We therefore addressed the impact of TCF7L2 isoforms on hepatocyte nuclear factor 4 (HNF4) and the regulation of gluconeogenesis genes.
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s00125-013-3154-z
Web End =10.1007/s00125-013-3154- z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
B. Neve : O. Le Bacquer : S. Caron : M. Huyvaert : A. Leloire :
O. Poulain-Godefroy : C. Lecoeur : F. Pattou : B. Staels : P. Froguel European Genomic Institute for Diabetes (EGID), Lille, France
B. Neve : O. Le Bacquer : S. Caron : M. Huyvaert : A. Leloire :
O. Poulain-Godefroy : C. Lecoeur : F. Pattou : B. Staels : P. Froguel University Lille 2 of Health and Law, Lille, France
B. Neve : S. Caron : M. Huyvaert : A. Leloire :
O. Poulain-Godefroy : C. Lecoeur : B. Staels : P. Froguel Institut Pasteur de Lille, Lille, France
B. Neve (*) : M. Huyvaert : A. Leloire : O. Poulain-Godefroy :
C. Lecoeur : P. FroguelCNRS, UMR8199, Gnomique et Maladies Mtaboliques, Institut de Biologie de Lille & Institut Pasteur de Lille, 1 Rue du Professeur Calmette, CS 50447, 59021 Lille Cedex, Francee-mail: [email protected]
O. Le Bacquer : F. PattouInserm, U859, Facult de Mdecine, Lille, France
S. Caron : B. StaelsInserm, UMR1011, Lille, France
P. FroguelDepartment of Genomics of Common Disease, School Of Public Health, Hammersmith Hospital, Imperial College, London, UK
Methods Liver TCF7L2 transcripts were analysed by quantitative PCR in 33 non-diabetic and 31 type 2 diabetic obese individuals genotyped for TCF7L2 rs7903146. To analyse transcriptional regulation by TCF7L2, small interfering RNA transfection, luciferase reporter and coimmunoprecipitation assays were performed in human hepatoma HepG2 cells.