Abstract：
BACKGROUND:Diabetes is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of preventive and therapeutic approaches. Genetic and environmental factors are the culprits involved in diabetes risk. Evidence from the last decade has highlighted that deregulation in the immune and inflammatory responses increase susceptibility to type 1 and type 2 diabetes. Spatiotemporal patterns of gene expression involved in immune cell polarisation depend on genomic enhancer elements in response to inflammatory and metabolic cues. Several studies have reported that most regulatory genetic variants are located in the non-protein coding regions of the genome and particularly in enhancer regions. The progress of high-throughput technologies has permitted the characterisation of enhancer chromatin properties. These advances support the concept that genetic alteration of enhancers may influence the immune and inflammatory responses in relation to diabetes. SCOPE OF REVIEW:Results from genome-wide association studies (GWAS) combined with functional and integrative analyses have elucidated the impacts of some diabetes risk-associated variants that are involved in the regulation of the immune system. Additionally, genetic variant mapping to enhancer regions may alter enhancer status, which in turn leads to aberrant expression of inflammatory genes associated with diabetes susceptibility. The focus of this review was to provide an overview of the current indications that inflammatory processes are regulated at the genetic and epigenomic levels in diabetes, along with perspectives on future research avenues that may improve understanding of the disease. MAJOR CONCLUSIONS:In this review, we provide genetic evidence in support of a deregulated immune response as a risk factor in diabetes. We also argue about the importance of enhancer regions in the regulation of immune cell polarisation and how the recent advances using genome-wide methods for enhancer identification have enabled the determination of the impact of enhancer genetic variation on diabetes onset and phenotype. This could eventually lead to better management plans and improved treatment responses in human diabetes.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Diedisheim M,Carcarino E,Vandiedonck C,Roussel R,Gautier JF,Venteclef Ndoi
10.1016/j.molmet.2020.101041subject
Has Abstractpub_date
2020-11-01 00:00:00pages
101041issn
2212-8778pii
S2212-8778(20)30115-0journal_volume
41pub_type
杂志文章,评审abstract：OBJECTIVE:Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS:To i...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.07.015
更新日期：2017-10-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.04.008
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.05.004
更新日期：2019-07-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.11.005
更新日期：2020-01-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.06.010
更新日期：2015-07-06 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.03.014
更新日期：2018-06-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.10.014
更新日期：2018-01-01 00:00:00
abstract：:Decreased β-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore β-cell mass and normoglycemia is to improve β-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2012.08.006
更新日期：2012-08-17 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.04.010
更新日期：2019-07-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.02.008
更新日期：2018-05-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.12.014
更新日期：2018-03-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2018.10.008
更新日期：2019-01-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2019.11.015
更新日期：2020-02-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.10.003
更新日期：2016-10-24 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2013.11.008
更新日期：2013-11-28 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.01.003
更新日期：2017-01-12 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101120
更新日期：2021-01-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.02.001
更新日期：2016-02-13 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101052
更新日期：2020-11-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.04.003
更新日期：2016-04-13 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2017.07.012
更新日期：2017-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.molmet.2017.10.006
更新日期：2017-12-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.01.002
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journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2015.12.006
更新日期：2016-01-14 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2013.10.006
更新日期：2013-10-23 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.08.003
更新日期：2018-11-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.03.009
更新日期：2017-03-27 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.10.003
更新日期：2018-12-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2016.12.006
更新日期：2016-12-21 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.06.002
更新日期：2015-06-15 00:00:00
