Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

Dayeh, Tasnim; Ling, Charlotte

doi:10.1139/bcb-2015-0057

Cited by 35 publications

(28 citation statements)

References 125 publications

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“…Therefore, histone modification enzymes have a highly specific role during the development and differentiation of different pancreatic cells. In addition, studies have shown that the HDAC inhibitor MC1568 can promote the expression of PDX4 and insulin (Dayeh and Ling, 2015 ). These results show that HDAC plays a key role in mediating pancreatic β cell differentiation and development.…”

Section: The Role Of Histone Modification In β Cell Differentiation Amentioning

confidence: 99%

RETRACTED: Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells

Liu

et al. 2020

Front. Cell Dev. Biol.

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Diabetes, a metabolic disease with multiple causes characterized by high blood sugar, has become a public health problem. Hyperglycaemia is caused by deficiencies in insulin secretion, impairment of insulin function, or both. The insulin secreted by pancreatic β cells is the only hormone in the body that lowers blood glucose levels and plays vital roles in maintaining glucose homeostasis. Therefore, investigation of the molecular mechanisms of pancreatic β cell differentiation and function is necessary to elucidate the processes involved in the onset of diabetes. Although numerous studies have shown that transcriptional regulation is essential for the differentiation and function of pancreatic β cells, increasing evidence indicates that epigenetic mechanisms participate in controlling the fate and regulation of these cells. Epigenetics involves heritable alterations in gene expression caused by DNA methylation, histone modification and non-coding RNA activity that does not result in DNA nucleotide sequence alterations. Recent research has revealed that a variety of epigenetic modifications play an important role in the development of diabetes. Here, we review the mechanisms by which epigenetic regulation affects β cell differentiation and function.

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Section: The Role Of Histone Modification In β Cell Differentiation Amentioning

confidence: 99%

RETRACTED: Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells

Liu

et al. 2020

Front. Cell Dev. Biol.

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“…Factors that contribute to compromised insulin secretion are not well known and may include epigenetic dysregulation, which is yet to be elucidated. 38 …”

Section: Discussionmentioning

confidence: 99%

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012

et al. 2017

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BACKGROUND Diagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001–2009 period, but data on recent incidence trends are lacking. METHODS We ascertained cases of type 1 and type 2 diabetes mellitus at five study centers in the United States. Denominators (4.9 million youths annually) were obtained from the U.S. Census or health-plan member counts. After the calculation of annual incidence rates for the 2002–2012 period, we analyzed trends using generalized autoregressive moving-average models with 2-year moving averages. RESULTS A total of 11,245 youths with type 1 diabetes (0 to 19 years of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified. Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4% annually (from 19.5 cases per 100,000 youths per year in 2002–2003 to 21.7 cases per 100,000 youths per year in 2011–2012, P = 0.03). In adjusted pairwise comparisons, the annual rate of increase was greater among Hispanics than among non-Hispanic whites (4.2% vs. 1.2%, P<0.001). Overall unadjusted incidence rates of type 2 diabetes increased by 7.1% annually (from 9.0 cases per 100,000 youths per year in 2002–2003 to 12.5 cases per 100,000 youths per year in 2011–2012, P<0.001 for trend across race or ethnic group, sex, and age subgroups). Adjusted pairwise comparisons showed that the relative annual increase in the incidence of type 2 diabetes among non-Hispanic whites (0.6%) was lower than that among non-Hispanic blacks, Asians or Pacific Islanders, and Native Americans (P<0.05 for all comparisons) and that the annual rate of increase among Hispanics differed significantly from that among Native Americans (3.1% vs. 8.9%, P = 0.01). After adjustment for age, sex, and race or ethnic group, the relative annual increase in the incidence of type 1 diabetes was 1.8% (P<0.001) and that of type 2 diabetes was 4.8% (P<0.001). CONCLUSIONS The incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002–2012 period, particularly among youths of minority racial and ethnic groups. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Centers for Disease Control and Prevention.)

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“…Second, DNA methylation was measured using DNA extracted from whole blood that was the only accessible type of sample and may not be representative of more disease-relevant tissues for the diseases under study, such as pancreatic cells and adipose tissues. Studies of methylation in obesity or T2D based on disease-relevant tissues such as the skeletal muscle, adipose tissue, or pancreatic islets are interesting but only exist for relatively small studies [ 8 , 13 , 28 , 31 , 32 , 35 , 36 , 41 , 46 ]. Since DNA methylation can be strongly tissue dependent and as our data was obtained from blood samples, for consistency, we only selected methylation probes for replication from EWAS studies that were also performed in the blood.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic associations of type 2 diabetes and BMI in an Arab population

et al. 2016

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BackgroundThe prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigenome-wide association studies (EWASs) have revealed significant associations of T2D, obesity, and BMI with DNA methylation. However, populations from the Middle East, where T2D and obesity rates are highest worldwide, have not been investigated so far.MethodsWe performed the first EWAS in an Arab population with T2D and BMI and attempted to replicate 47 EWAS associations previously reported in Caucasians. We used the Illumina Infinium HumanMethylation450 BeadChip to quantify DNA methylation in whole blood DNA from 123 subjects of 15 multigenerational families from Qatar. To investigate the effect of differing genetic background and environment on the epigenetic associations, we further assessed the effect of replicated loci in 810 twins from UK.ResultsOur EWAS suggested a novel association between T2D and cg06721411 (DQX1; p value = 1.18 × 10−9). We replicated in the Qatari population seven CpG associations with BMI (SOCS3, p value = 3.99 × 10−6; SREBF1, p value = 4.33 × 10−5; SBNO2, p value = 5.87 × 10−5; CPT1A, p value = 7.99 × 10−5; PRR5L, p value = 1.85 × 10−4; cg03078551, intergenic region on chromosome 17; p value = 1.00 × 10−3; LY6G6E, p value = 1.10 × 10−3) and one with T2D (TXNIP, p value = 2.46 × 10−5). All the associations were further confirmed in the UK cohort for both BMI and T2D. Meta-analysis increased the significance of the observed associations and revealed strong heterogeneity of the effect sizes (apart from CPT1A), although associations at these loci showed concordant direction in the two populations.ConclusionsOur study replicated eight known CpG associations with T2D or BMI in an Arab population. Heterogeneity of the effects at all loci except CPT1A between the Qatari and UK studies suggests that the underlying mechanisms might depend on genetic background and environmental pressure. Our EWAS results provide a basis for comparison with other ethnicities.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0177-6) contains supplementary material, which is available to authorized users.

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Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

Cited by 35 publications

References 125 publications

RETRACTED: Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells

RETRACTED: Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012

Epigenetic associations of type 2 diabetes and BMI in an Arab population

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