Document Detail

Developmental and environmental epigenetic programming of the endocrine pancreas: consequences for type 2 diabetes.
MedLine Citation:
PMID:  23463236     Owner:  NLM     Status:  MEDLINE    
The development of the endocrine pancreas is controlled by a hierarchical network of transcriptional regulators. It is increasingly evident that this requires a tightly interconnected epigenetic "programme" to drive endocrine cell differentiation and maintain islet function. Epigenetic regulators such as DNA and histone-modifying enzymes are now known to contribute to determination of pancreatic cell lineage, maintenance of cellular differentiation states, and normal functioning of adult pancreatic endocrine cells. Persistent effects of an early suboptimal environment, known to increase risk of type 2 diabetes in later life, can alter the epigenetic control of transcriptional master regulators, such as Hnf4a and Pdx1. Recent genome-wide analyses also suggest that an altered epigenetic landscape is associated with the β cell failure observed in type 2 diabetes and aging. At the cellular level, epigenetic mechanisms may provide a mechanistic link between energy metabolism and stable patterns of gene expression. Key energy metabolites influence the activity of epigenetic regulators, which in turn alter transcription to maintain cellular homeostasis. The challenge is now to understand the detailed molecular mechanisms that underlie these diverse roles of epigenetics, and the extent to which they contribute to the pathogenesis of type 2 diabetes. In-depth understanding of the developmental and environmental epigenetic programming of the endocrine pancreas has the potential to lead to novel therapeutic approaches in diabetes.
Ionel Sandovici; Constanze M Hammerle; Susan E Ozanne; Miguel Constância
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2013-03-06
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  70     ISSN:  1420-9071     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-12     Completed Date:  2013-06-13     Revised Date:  2014-07-22    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1575-95     Citation Subset:  IM    
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MeSH Terms
Diabetes Mellitus, Type 2 / genetics*,  pathology
Epigenesis, Genetic*
Gene Expression Regulation, Developmental
Gene-Environment Interaction
Islets of Langerhans / growth & development*,  metabolism*,  pathology
Grant Support
BB/D007909/1//Biotechnology and Biological Sciences Research Council; BB/F015364/1//Biotechnology and Biological Sciences Research Council; FS/09/029/27902//British Heart Foundation; //Biotechnology and Biological Sciences Research Council; //British Heart Foundation; //Medical Research Council

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