Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin

被引：20

作者：

Ahlzen, Maja ^{[1
]}

Johansson, Lovisa E. ^{[1
]}

Cervin, Camilla ^{[1
]}

Tornqvist, Hans ^{[1
]}

Groop, Leif ^{[1
]}

Ridderstrale, Martin ^{[1
]}

机构：

[1] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Malmo Clin Obes, CRC, S-20502 Malmo, Sweden

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 370卷 / 01期

关键词：

TCF7L2; insulin resistance; adipocytes; type 2 diabetes mellitus; obesity; expression; genotyping;

D O I：

10.1016/j.bbrc.2008.03.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong association with type 2 diabetes with two defined risk haplotypes, HapA and HapB(T2D)). TCF7L2 may play a role in both glucose homeostasis and adipogenesis. Our aim was to characterize the TCF7L2 mRNA expression and regulation in human adipose tissue. We quantified TCF7L2 mRNA levels in cultured human adipocytes and in biopsies from visceral (VAT) and subcutaneous (SAT) adipose tissue from 38 obese non-diabetic subjects, using real-time PCR. The influence of haplotype and clinical traits on TCF7L2 mRNA levels were investigated. In vitro, insulin decreased TCF7L2 mRNA expression. This effect was attenuated in cells incubated with the free fatty acids palmitate or oleate. In vivo, we found significantly higher expression in SAT from more insulin resistant subjects. No correlations between TCF7L2 mRNA expression and obesity measures were observed. TCF7L2 expression was higher in VAT than in SAT and when stratifying for haplotype, this difference was seen in HapA carriers but not in non-HapA carriers. In conclusion, TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in insulin resistant subjects and in HapA carriers. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：49 / 52

页数：4

共 19 条

[1] Transcription factor TCF7L2 genetic study in the French population -: Expression in human β-cells and adipose tissue and strong association with type 2 diabetes [J].

Cauchi, Stephane ;

Meyre, David ;

Dina, Christian ;

Choquet, Helene ;

Samson, Chantal ;

Gallina, Sophie ;

Balkau, Beverley ;

Charpentier, Guillaume ;

Pattou, Francois ;

Stetsyuk, Volodymyr ;

Scharfmann, Raphael ;

Staels, Bart ;

Fruhbeck, Gema ;

Froguel, Philippe .

DIABETES, 2006, 55 (10) :2903-2908

[2] Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population [J].

Chandak, G. R. ;

Janipalli, C. S. ;

Bhaskar, S. ;

Kulkarni, S. R. ;

Mohankrishna, P. ;

Hattersley, A. T. ;

Frayling, T. M. ;

Yajnik, C. S. .

DIABETOLOGIA, 2007, 50 (01) :63-67

[3] Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish -: Replication and evidence for a role in both insulin secretion and insulin resistance [J].

Damcott, Coleen M. ;

Pollin, Toni I. ;

Reinhart, Laurie J. ;

Ott, Sandra H. ;

Shen, Haiqing ;

Silver, Kristi D. ;

Mitchell, Braxton D. ;

Shuldiner, Alan R. .

DIABETES, 2006, 55 (09) :2654-2659

[4] Abdominal obesity and metabolic syndrome [J].

Despres, Jean-Pierre ;

Lemieux, Isabelle .

NATURE, 2006, 444 (7121) :881-887

[5] Transcription factor 7-like 2 polymorphisms and type 2 diabetes, glucose homeostasis traits and gene expression in US participants of European and African descent [J].

Elbein, S. C. ;

Chu, W. S. ;

Das, S. K. ;

Yao-Borengasser, A. ;

Hasstedt, S. J. ;

Wang, H. ;

Rasouli, N. ;

Kern, P. A. .

DIABETOLOGIA, 2007, 50 (08) :1621-1630

[6] TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program [J].

Florez, Jose C. ;

Jablonski, Kathleen A. ;

Bayley, Nick ;

Pollin, Toni I. ;

de Bakker, Paul I. W. ;

Shuldiner, Alan R. ;

Knowler, William C. ;

Nathan, David M. ;

Altshuler, David .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (03) :241-250

[7] Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes [J].

Grant, SFA ;

Thorleifsson, G ;

Reynisdottir, I ;

Benediktsson, R ;

Manolescu, A ;

Sainz, J ;

Helgason, A ;

Stefansson, H ;

Emilsson, V ;

Helgadottir, A ;

Styrkarsdottir, U ;

Magnusson, KP ;

Walters, GB ;

Palsdottir, E ;

Jonsdottir, T ;

Gudmundsdottir, T ;

Gylfason, A ;

Saemundsdottir, J ;

Wilensky, RL ;

Reilly, MP ;

Rader, DJ ;

Bagger, Y ;

Christiansen, C ;

Gudnason, V ;

Sigurdsson, G ;

Thorsteinsdottir, U ;

Gulcher, JR ;

Kong, A ;

Stefansson, K .

NATURE GENETICS, 2006, 38 (03) :320-323

[8] Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution [J].

Helgason, Agnar ;

Palsson, Snaebjorn ;

Thorleifsson, Gudmar ;

Grant, Struan F. A. ;

Emilsson, Valur ;

Gunnarsdottir, Steinunn ;

Adeyemo, Adebowale ;

Chen, Yuanxiu ;

Chen, Guanjie ;

Reynisdottir, Inga ;

Benediktsson, Rafn ;

Hinney, Anke ;

Hansen, Torben ;

Andersen, Gitte ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Schaefer, Helmut ;

Faruque, Mezbah ;

Doumatey, Ayo ;

Zhou, Jie ;

Wilensky, Robert L. ;

Reilly, Muredach P. ;

Rader, Daniel J. ;

Bagger, Yu ;

Christiansen, Claus ;

Sigurdsson, Gunnar ;

Hebebrand, Johannes ;

Pedersen, Oluf ;

Thorsteinsdottir, Unnur ;

Gulcher, Jeffrey R. ;

Kong, Augustine ;

Rotimi, Charles ;

Stefansson, Kari .

NATURE GENETICS, 2007, 39 (02) :218-225

[9] New aspects of Wnt signaling pathways in higher vertebrates [J].

Huelsken, J ;

Birchmeier, W .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2001, 11 (05) :547-553

[10] Variation in the adiponutrin gene influences its expression and associates with obesity [J].

Johansson, LE ;

Hoffstedt, J ;

Parikh, H ;

Carlsson, E ;

Wabitsch, M ;

Bondeson, AG ;

Hedenbro, J ;

Tornqvist, H ;

Groop, L ;

Ridderstråle, M .

DIABETES, 2006, 55 (03) :826-833

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