Reading between the (Genetic) Lines: How Epigenetics is Unlocking Novel Therapies for Type 1 Diabetes

被引:7
作者
Akil, Ammira-Sarah AL-Shabeeb [1 ]
Jerman, Laila F. [1 ]
Yassin, Esraa [1 ]
Padmajeya, Sujitha S. [1 ]
Al-Kurbi, Alya [1 ]
Fakhro, Khalid A. [1 ,2 ,3 ]
机构
[1] Sidra Med, Dept Human Genet, POB 26999, Doha, Qatar
[2] Weill Cornell Med Coll, Dept Genet Med, POB 24144, Doha, Qatar
[3] Hamad Bin Khalifa Univ, Coll Hlth & Life Sci, POB 34110, Doha, Qatar
关键词
chromatin; DNA methylation; epigenetics; histone modifications; metaboloepigenetics; miRNA; therapy; type; 1; diabetes; BETA-CELL PROLIFERATION; DNA METHYLATION; GLUCOSE-HOMEOSTASIS; MICRORNAS; EXPRESSION; RISK; APOPTOSIS; PROFILES; FIBROBLASTS; LYMPHOCYTES;
D O I
10.3390/cells9112403
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Type 1 diabetes (T1D) is an autoimmune condition where the body's immune cells destroy their insulin-producing pancreatic beta cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well established that genetic and environmental factors contribute to the initiation and progression of T1D, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with T1D pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage T1D.
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页数:14
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共 79 条
  • [1] Type 1 diabetes
    Atkinson, Mark A.
    Eisenbarth, George S.
    Michels, Aaron W.
    [J]. LANCET, 2014, 383 (9911) : 69 - 82
  • [2] DNA methylation and its role in the pathogenesis of diabetes
    Bansal, Amita
    Pinney, Sara E.
    [J]. PEDIATRIC DIABETES, 2017, 18 (03) : 167 - 177
  • [3] Epigenetic effects of metformin: From molecular mechanisms to clinical implications
    Bridgeman, Stephanie Claire
    Ellison, Gaewyn Colleen
    Melton, Phillip Edward
    Newsholme, Philip
    Mamotte, Cyril Desire Sylvain
    [J]. DIABETES OBESITY & METABOLISM, 2018, 20 (07) : 1553 - 1562
  • [4] Histone ubiquitination and deubiquitination in transcription DNA damage response, and cancer
    Cao, Jian
    Yan, Qin
    [J]. FRONTIERS IN ONCOLOGY, 2012, 2
  • [5] Gene Expression Differences in Skin Fibroblasts in Identical Twins Discordant for Type 1 Diabetes
    Caramori, M. Luiza
    Kim, Youngki
    Moore, Jason H.
    Rich, Stephen S.
    Mychaleckyj, Josyf C.
    Kikyo, Nobuaki
    Mauer, Michael
    [J]. DIABETES, 2012, 61 (03) : 739 - 744
  • [6] Epigenetics of discordant monozygotic twins: implications for disease
    Castillo-Fernandez, Juan E.
    Spector, Tim D.
    Bell, Jordana T.
    [J]. GENOME MEDICINE, 2014, 6
  • [8] Converting Adult Pancreatic Islet α Cells into β Cells by Targeting Both Dnmt1 and Arx
    Chakravarthy, Harini
    Gu, Xueying
    Enge, Martin
    Dai, Xiaoqing
    Wang, Yong
    Damond, Nicolas
    Downie, Carolina
    Liu, Kathy
    Wang, Jing
    Xing, Yuan
    Chera, Simona
    Thorel, Fabrizio
    Quake, Stephen
    Oberholzer, Jose
    MacDonald, Patrick E.
    Herrera, Pedro L.
    Kim, Seung K.
    [J]. CELL METABOLISM, 2017, 25 (03) : 622 - 634
  • [9] Application of microRNAs in diabetes mellitus
    Chen, Haiyong
    Lan, Hui-Yao
    Roukos, Dimitrios H.
    Cho, William C.
    [J]. JOURNAL OF ENDOCRINOLOGY, 2014, 222 (01) : R1 - R10
  • [10] Lysine deacetylase inhibition prevents diabetes by chromatin-independent immunoregulation and β-cell protection
    Christensen, Dan Ploug
    Gysemans, Conny
    Lundh, Morten
    Dahllof, Mattias Salling
    Noesgaard, Daniel
    Schmidt, Soren Fisker
    Mandrup, Susanne
    Birkbak, Nikolai
    Workman, Christopher T.
    Piemonti, Lorenzo
    Blaabjerg, Lykke
    Monzani, Valmen
    Fossati, Gianluca
    Mascagni, Paolo
    Paraskevas, Steven
    Aikin, Reid A.
    Billestrup, Nils
    Grunnet, Lars Groth
    Dinarello, Charles A.
    Mathieu, Chantal
    Mandrup-Poulsen, Thomas
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (03) : 1055 - 1059