Current Understanding on Role of the Wnt Signaling Pathway Effector TCF7L2 in Glucose Homeostasis

被引：82

作者：

Jin, Tianru ^{[1
]}

机构：

[1] Univ Hlth Network, Toronto Gen Res Inst, Div Adv Diagnost, Toronto, ON M5G 2C4, Canada

来源：

ENDOCRINE REVIEWS | 2016年 / 37卷 / 03期

基金：

加拿大健康研究院;

关键词：

TYPE-2; DIABETES-MELLITUS; SINGLE NUCLEOTIDE POLYMORPHISMS; PROGLUCAGON GENE-EXPRESSION; LIVER-SPECIFIC EXPRESSION; BETA-CELL REGENERATION; 7-LIKE; TCF7L2; TRANSCRIPTION FACTOR; SUSCEPTIBILITY GENE; OXIDATIVE STRESS; ADIPOSE-TISSUE;

D O I：

10.1210/er.2015-1146

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The role of the Wnt signaling pathway in metabolic homeostasis has drawn our intensive attention, especially after the genome-wide association study discovery that certain polymorphisms of its key effector TCF7L2 are strongly associated with the susceptibility to type 2 diabetes. For a decade, great efforts have been made in determining the function of TCF7L2 in various metabolic organs, which have generated both considerable achievements and disputes. In this review, I will briefly introduce the canonical Wnt signaling pathway, focusing on its effector beta-catenin/TCF, including emphasizing the bidirectional feature of TCFs and beta-catenin post-translational modifications. I will then summarize the observations on the association between TCF7L2 polymorphisms and type 2 diabetes risk. The main content, however, is on the intensive functional exploration of the metabolic role of TCF7L2, including the disputes generated on determining its role in the pancreas and liver with various transgenic mouse lines. Finally, I will discuss those achievements and disputes and present my future perspectives.

引用

页码：254 / 277

页数：24

共 214 条

[61] PCAF Acetylates β-Catenin and Improves Its Stability [J].

Ge, Xinjian ;

Jin, Qihuang ;

Zhang, Fang ;

Yan, Tingting ;

Zhai, Qiwei .

MOLECULAR BIOLOGY OF THE CELL, 2009, 20 (01) :419-427

[62] Organ Patterning in the Adult Stage: The Role of Wnt/β-Catenin Signaling in Liver Zonation and Beyond [J].

Gebhardt, Rolf ;

Hovhannisyan, Amalya .

DEVELOPMENTAL DYNAMICS, 2010, 239 (01) :45-55

[63] Large-scale association studies of variants in genes encoding the pancreatic β-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes [J].

Gloyn, AL ;

Weedon, MN ;

Owen, KR ;

Turner, MJ ;

Knight, BA ;

Hitman, G ;

Walker, M ;

Levy, JC ;

Sampson, M ;

Halford, S ;

McCarthy, MI ;

Hattersley, AT ;

Frayling, TM .

DIABETES, 2003, 52 (02) :568-572

[64] The Combined Hyperlipidemia Caused by Impaired Wnt-LRP6 Signaling Is Reversed by Wnt3a Rescue [J].

Go, Gwang-Woong ;

Srivastava, Roshni ;

Hernandez-Ono, Antonio ;

Gang, Gyoungok ;

Smith, Stephen B. ;

Booth, Carmen J. ;

Ginsberg, Henry N. ;

Mani, Arya .

CELL METABOLISM, 2014, 19 (02) :209-220

[65]

Go Gwang-woong, 2012, Yale Journal of Biology and Medicine, V85, P19

[66] The human frizzled 6 (HFz6) acts as a negative regulator of the canonical Wnt•β-Catenin signaling cascade [J].

Golan, T ;

Yaniv, A ;

Bafico, A ;

Liu, GZ ;

Gazit, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) :14879-14888

[67] LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development [J].

Gong, YQ ;

Slee, RB ;

Fukai, N ;

Rawadi, G ;

Roman-Roman, S ;

Reginato, AM ;

Wang, HW ;

Cundy, T ;

Glorieux, FH ;

Lev, D ;

Zacharin, M ;

Oexle, K ;

Marcelino, J ;

Suwairi, W ;

Heeger, S ;

Sabatakos, G ;

Apte, S ;

Adkins, WN ;

Allgrove, J ;

Arslan-Kirchner, M ;

Batch, JA ;

Beighton, P ;

Black, GCM ;

Boles, RG ;

Boon, LM ;

Borrone, C ;

Brunner, HG ;

Carle, GF ;

Dallapiccola, B ;

De Paepe, A ;

Floege, B ;

Halfhide, ML ;

Hall, B ;

Hennekam, RC ;

Hirose, T ;

Jans, A ;

Jüppner, H ;

Kim, CA ;

Keppler-Noreuil, K ;

Kohlschuetter, A ;

LaCombe, D ;

Lambert, M ;

Lemyre, E ;

Letteboer, T ;

Peltonen, L ;

Ramesar, RS ;

Romanengo, M ;

Somer, H ;

Steichen-Gersdorf, E ;

Steinmann, B .

CELL, 2001, 107 (04) :513-523

[68] Wnt signaling: Multiple pathways, multiple receptors, and multiple transcription factors [J].

Gordon, Michael D. ;

Nusse, Roel .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (32) :22429-22433

[69] 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

[70] Association analysis of 6,736 UK subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk [J].

Groves, Christopher J. ;

Zeggini, Eleftheria ;

Minton, Jayne ;

Frayling, Timothy M. ;

Weedon, Michael N. ;

Rayner, Nigel W. ;

Hitman, Graham A. ;

Walker, Mark ;

Wiltshire, Steven ;

Hattersley, Andrew T. ;

McCarthy, Mark I. .

DIABETES, 2006, 55 (09) :2640-2644

← 2 3 4 5 6 7 8 9 10 11 →