The inflammatory effect of epigenetic factors and modifications in type 2 diabetes

Akbari, M; Hassan‐Zadeh, Vahideh

doi:10.1007/s10787-019-00663-9

Cited by 18 publications

(14 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies have demonstrated that intrauterine growth restriction is associated with epigenetic changes in different tissues of the offspring [18,[128][129][130][131][132][133][134][135][136], and several implicate epigenetic mechanisms in pancreatic β-cell failure and development of T2D [13,15,17,135,[137][138][139][140]. In our IUGR model, we have previously demonstrated in adult rats that IUGR induces genome-wide changes in DNA methylation at key loci in islets [23].…”

Section: Discussionmentioning

confidence: 84%

Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

Lien

Wang

et al. 2020

Cells

View full text Add to dashboard Cite

Intrauterine growth retardation (IUGR), which induces epigenetic modifications and permanent changes in gene expression, has been associated with the development of type 2 diabetes. Using a rat model of IUGR, we performed ChIP-Seq to identify and map genome-wide histone modifications and gene dysregulation in islets from 2- and 10-week rats. IUGR induced significant changes in the enrichment of H3K4me3, H3K27me3, and H3K27Ac marks in both 2-wk and 10-wk islets, which were correlated with expression changes of multiple genes critical for islet function in IUGR islets. ChIP-Seq analysis showed that IUGR-induced histone mark changes were enriched at critical transcription factor binding motifs, such as C/EBPs, Ets1, Bcl6, Thrb, Ebf1, Sox9, and Mitf. These transcription factors were also identified as top upstream regulators in our previously published transcriptome study. In addition, our ChIP-seq data revealed more than 1000 potential bivalent genes as identified by enrichment of both H3K4me3 and H3K27me3. The poised state of many potential bivalent genes was altered by IUGR, particularly Acod1, Fgf21, Serpina11, Cdh16, Lrrc27, and Lrrc66, key islet genes. Collectively, our findings suggest alterations of histone modification in key transcription factors and genes that may contribute to long-term gene dysregulation and an abnormal islet phenotype in IUGR rats.

show abstract

Section: Discussionmentioning

confidence: 84%

Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

Lien

Wang

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…N-terminal tails of histones are subject to various post-translational modifications including: acetylation, methylation, and ubiquitinoylation of lysine (K), methylation of arginine (R), and phosphorylation of serine (S) and threonine (T) (12), that can impact gene expression by altering chromatin structure or recruiting histone modifiers. The state of the chromatin structure is regulated by histone-modifying enzymes, which chemically change histone tail residues (13).…”

Section: The Major Classes Of Epigenetic Modification and Their Roles In Regulating B Cell Dysfunction Chromatin Modifications And Accessmentioning

confidence: 99%

“…Acetylation of lysine on histone tails removes the positive charge on the histones to weaken the interaction between the positively-charged histones and the negatively-charged DNA. The lysine acetylation also creates docking sites for reader proteins in addition to increased accessibility of chromatin for transcription factor (TF) binding resulting in downstream gene expression changes (13). The acetylation of histones have been associated with islet development, function, and the development of T2DM.…”

Section: The Major Classes Of Epigenetic Modification and Their Roles In Regulating B Cell Dysfunction Chromatin Modifications And Accessmentioning

confidence: 99%

Epigenetic Regulation of β Cell Identity and Dysfunction

et al. 2021

View full text Add to dashboard Cite

β cell dysfunction and failure are driving forces of type 2 diabetes mellitus (T2DM) pathogenesis. Investigating the underlying mechanisms of β cell dysfunction may provide novel targets for the development of next generation therapy for T2DM. Epigenetics is the study of gene expression changes that do not involve DNA sequence changes, including DNA methylation, histone modification, and non-coding RNAs. Specific epigenetic signatures at all levels, including DNA methylation, chromatin accessibility, histone modification, and non-coding RNA, define β cell identity during embryonic development, postnatal maturation, and maintain β cell function at homeostatic states. During progression of T2DM, overnutrition, inflammation, and other types of stress collaboratively disrupt the homeostatic epigenetic signatures in β cells. Dysregulated epigenetic signatures, and the associating transcriptional outputs, lead to the dysfunction and eventual loss of β cells. In this review, we will summarize recent discoveries of the establishment and disruption of β cell-specific epigenetic signatures, and discuss the potential implication in therapeutic development.

show abstract

“…These examples underline that hyperglycemia induce an overexpression of proinflammatory genes by redundant epigenetic histone marks, that in the case of NF-kB, additionally involve acetylation of lysine residues of transcription factor itself (51). Other relevant overexpression states of proinflammatory genes mediated by methylation changes related to hyperglycemic stimulus are the IL-6 and MCP-1 in vascular smooth muscle cells, IL-6 in rat cardiomyocytes, IL-12 subunit beta (IL-12B), macrophage inflammatory protein (MIP)-1a, MIP-1b, and IL-6 in THP-1 monocytes (52).…”

Section: Histone Tail Modificationsmentioning

confidence: 99%

“…The higher levels of miR-125b triggers a decrease in the SUV39H1 histone methylase levels, leading to a reduction of the H3K9 activating signal in the promoters of IL-6 and MCP-1 (53). Other m i R N A s u p r e g u l a t i o n s i n T 2 D M i m p a c t i n g t h e proinflammatory genes expression are: miR-146a decreasing the expression TNF receptor-associated factor 6 (TRAF6) and interleukin 1 receptor-associated kinase 1 (IRAK1); miR-200c family members increasing the expression of COX-2 and MCP-1; and miR-504 increasing the expression of IL-6, COX2 and MCP-1 (52). Abnormalities of lncRNA have also been observed in T2DM-associated inflammation.…”

Section: Non-coding Rnamentioning

confidence: 99%

Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus

et al. 2021

View full text Add to dashboard Cite

Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.

show abstract

The inflammatory effect of epigenetic factors and modifications in type 2 diabetes

Cited by 18 publications

References 147 publications

Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

Altered Transcription Factor Binding and Gene Bivalency in Islets of Intrauterine Growth Retarded Rats

Epigenetic Regulation of β Cell Identity and Dysfunction

Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus

Contact Info

Product

Resources

About