Book ChapterDOI
Wnt Signaling in Pancreatic Islets
Zhengyu Liu,Joel F. Habener +1 more
TLDR
In this paper, a review focused on the hormonal regulation of Wnt signaling in islets and implications for mutations in components of the Wnt signalling pathway as a source for risk-associated alleles for type 2 diabetes.Abstract:
The Wnt signaling pathway is critically important not only for stem cell amplification, differentiation, and migration, but also is important for organogenesis and the development of the body plan. Beta-catenin/TCF7L2-dependent Wnt signaling (the canonical pathway) is involved in pancreas development, islet function, and insulin production and secretion. The glucoincretin hormone glucagon-like peptide-1 and the chemokine stromal cell-derived factor-1 modulate canonical Wnt signaling in β-cells which is obligatory for their mitogenic and cytoprotective actions. Genome-wide association studies have uncovered 19 gene loci that confer susceptibility for the development of type 2 diabetes. At least 14 of these diabetes risk alleles encode proteins that are implicated in islet growth and functioning. Seven of them are either components of, or known target genes for, Wnt signaling. The transcription factor TCF7L2 is particularly strongly associated with risk for diabetes and appears to be fundamentally important in both canonical Wnt signaling and β-cell functioning. Experimental loss of TCF7L2 function in islets and polymorphisms in TCF7L2 alleles in humans impair glucose-stimulated insulin secretion, suggesting that perturbations in the Wnt signaling pathway may contribute substantially to the susceptibility for, and pathogenesis of, type 2 diabetes. This review focuses on considerations of the hormonal regulation of Wnt signaling in islets and implications for mutations in components of the Wnt signaling pathway as a source for risk-associated alleles for type 2 diabetes.read more
Citations
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Journal ArticleDOI
Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
Karl Bacos,Linn Gillberg,Petr Volkov,Anders H. Olsson,Torben Hansen,Oluf Pedersen,Anette P. Gjesing,Hans Eiberg,Tiinamaija Tuomi,Peter Almgren,Leif Groop,Lena Eliasson,Allan Vaag,Tasnim Dayeh,Charlotte Ling +14 more
TL;DR: It is demonstrated that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.
Journal ArticleDOI
New-Onset Diabetes After Renal Transplantation: Risk assessment and management
TL;DR: The factors contributing to the risk of NODAT and the strategies related to modifiable factors are reviewed and recognition of these factors may help clinicians to evaluate prospectively appropriate prevention strategies to minimize the risk.
Journal ArticleDOI
Understanding human fetal pancreas development using subpopulation sorting, RNA sequencing and single-cell profiling.
Cyrille Ramond,Cyrille Ramond,Cyrille Ramond,Belin Selcen Beydag-Tasöz,Ajuna Azad,Martijn van de Bunt,Martijn van de Bunt,Martijn van de Bunt,Maja Borup Kjær Petersen,Maja Borup Kjær Petersen,Nicola L. Beer,Nicolas Glaser,Nicolas Glaser,Nicolas Glaser,Claire Berthault,Claire Berthault,Claire Berthault,Anna L. Gloyn,Anna L. Gloyn,Mattias Hansson,Mark I. McCarthy,Mark I. McCarthy,Christian Honoré,Anne Grapin-Botton,Raphael Scharfmann,Raphael Scharfmann,Raphael Scharfmann +26 more
TL;DR: This study develops sorting strategies to isolate specific pancreatic populations and uses single-cell profiling to evaluate how well individual pancreatic cells derived in vitro from human pluripotent stem cells mirror the natural process occurring in human fetuses.
Journal ArticleDOI
TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass
Iseki Takamoto,Naoto Kubota,Keizo Nakaya,Katsuyoshi Kumagai,Katsuyoshi Kumagai,Shinji Hashimoto,Tetsuya Kubota,Mariko Inoue,Eiji Kajiwara,Hisayuki Katsuyama,Atsushi Obata,Yoshitaka Sakurai,Masahiko Iwamoto,Tadahiro Kitamura,Kohjiro Ueki,Takashi Kadowaki +15 more
TL;DR: TCF7L2 expressed in the pancreatic beta cells plays a crucial role in glucose metabolism through regulation of the beta cell mass and is investigated for its role in insulin secretion in vivo.
Journal ArticleDOI
Low Density Lipoprotein (LDL) Receptor-related Protein 6 (LRP6) Regulates Body Fat and Glucose Homeostasis by Modulating Nutrient Sensing Pathways and Mitochondrial Energy Expenditure
Wenzhong Liu,Rajvir Singh,Cheol Soo Choi,Cheol Soo Choi,Hui-Young Lee,Ali R. Keramati,Varman T. Samuel,Richard P. Lifton,Gerald I. Shulman,Arya Mani +9 more
TL;DR: This study identifies LRP6 as a nutrient-sensitive regulator of body weight and glucose metabolism and as a potential target for pharmacological interventions in obesity and diabetes.
References
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Journal ArticleDOI
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Journal ArticleDOI
A genome-wide association study identifies novel risk loci for type 2 diabetes
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Journal ArticleDOI
Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels
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TL;DR: The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
Journal ArticleDOI
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
Laura J. Scott,Karen L. Mohlke,Lori L. Bonnycastle,Cristen J. Willer,Yun Li,William L. Duren,Michael R. Erdos,Heather M. Stringham,Peter S. Chines,Anne U. Jackson,Ludmila Prokunina-Olsson,Chia-Jen Ding,Amy J. Swift,Narisu Narisu,Tianle Hu,Randall Pruim,Rui Xiao,Xiao-Yi Li,Karen N. Conneely,Nancy Riebow,Andrew G. Sprau,Maurine Tong,Peggy P. White,Kurt N. Hetrick,Michael W. Barnhart,Craig W. Bark,Janet L. Goldstein,Lee Watkins,Fang Xiang,Jouko Saramies,Thomas A. Buchanan,Richard M. Watanabe,Timo T. Valle,Leena Kinnunen,Gonçalo R. Abecasis,Elizabeth W. Pugh,Kimberly F. Doheny,Richard N. Bergman,Jaakko Tuomilehto,Francis S. Collins,Michael Boehnke +40 more
TL;DR: The number of T2D loci now confidently identified to at least 10 is confirmed, and it is confirmed that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T1D risk.
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