DNA methylation landscapes in the pathogenesis of type 2 diabetes mellitus

AbstractThis study was performed to elucidate the potential influence of He Qi San (HQS) on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients with phlegm-blood stasis syndrome (PBSS), and to determine DNA methylation changes. Sixty T2DM patients with PBSS were randomly divided into control and HQS groups. The control group received conventional treatments, and the HQS group received conventional treatments plus HQS. Glucose metabolism (FPG, 2hPG, FINS, and HbA1c) and lipid metabolism indexes (TG, TC and LDL-C) were determined. Genes with differential DNA methylation were subjected to GO and KEGG analyses. Glucose and lipid metabolism indexes in both groups were reduced, but were much more pronounced in the HQS group. Differential promoter CpG methylation regions were identified in 682 genes, including 426 genes with high-CpG promoters, 150 genes with intermediate CpG promoters, and 106 genes with low CpG promoters. Genes with differential DNA methylation were mainly enriched in the AMPK and insulin signaling pathways, terpenoid backbone biosynthesis, and renin secretion. We concluded that HQS remarkably improved indexes of glucose and lipid metabolism in T2DM patients with PBSS through regulating the DNA methylation of genes in the AMPK and insulin signaling pathways and terpenoid backbone biosynthesis.

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Increased PARylation impacts the DNA methylation process in type 2 diabetes mellitus

Clinical Epigenetics ◽

10.1186/s13148-021-01099-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Michele Zampieri ◽

Maria Giulia Bacalini ◽

Ilaria Barchetta ◽

Stefania Scalea ◽

Flavia Agata Cimini ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus ◽

Cytosine Methylation ◽

Methylation Pattern ◽

Post Translational Modification ◽

Site Specific ◽

Dna Methylation Pattern

Abstract Background Epigenetic modifications, such as DNA methylation, can influence the genetic susceptibility to type 2 diabetes mellitus (T2DM) and the progression of the disease. Our previous studies demonstrated that the regulation of the DNA methylation pattern involves the poly(ADP-ribosyl)ation (PARylation) process, a post-translational modification of proteins catalysed by the poly(ADP-ribose) polymerase (PARP) enzymes. Experimental data showed that the hyperactivation of PARylation is associated with impaired glucose metabolism and the development of T2DM. Aims of this case–control study were to investigate the association between PARylation and global and site-specific DNA methylation in T2DM and to evaluate metabolic correlates. Results Data were collected from 61 subjects affected by T2DM and 48 healthy individuals, recruited as controls. Global levels of poly(ADP-ribose) (PAR, a surrogate of PARP activity), cytosine methylation (5-methylcytosine, 5mC) and de-methylation intermediates 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were determined in peripheral blood cells by ELISA-based methodologies. Site-specific DNA methylation profiling of SOCS3, SREBF1 and TXNIP candidate genes was performed by mass spectrometry-based bisulfite sequencing, methyl-sensitive endonucleases digestion and by DNA immuno-precipitation. T2DM subjects presented higher PAR levels than controls. In T2DM individuals, increased PAR levels were significantly associated with higher HbA1c levels and the accumulation of the de-methylation intermediates 5hmC and 5fC in the genome. In addition, T2DM patients with higher PAR levels showed reduced methylation with increased 5hmC and 5fC levels in specific SOCS3 sites, up-regulated SOCS3 expression compared to both T2DM subjects with low PAR levels and controls. Conclusions This study demonstrates the activation of PARylation processes in patients with T2DM, particularly in those with poor glycaemic control. PARylation is linked to dysregulation of DNA methylation pattern via activation of the DNA de-methylation cascade and may be at the basis of the differential gene expression observed in presence of diabetes.

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Association between DNA methylation of SORL1 5′-flanking region and mild cognitive impairment in type 2 diabetes mellitus

Annales d Endocrinologie ◽

10.1016/j.ando.2016.02.008 ◽

2016 ◽

Vol 77 (6) ◽

pp. 625-632 ◽

Cited By ~ 1

Author(s):

Yang Yu ◽

Wang Mingjiao ◽

Xiaohui Yang ◽

Miao Sui ◽

Tao Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Flanking Region

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Expression and DNA methylation status of microRNA-375 in patients with type 2 diabetes mellitus

Molecular Medicine Reports ◽

10.3892/mmr.2013.1872 ◽

2013 ◽

Vol 9 (3) ◽

pp. 967-972 ◽

Cited By ~ 31

Author(s):

KAN SUN ◽

XIANGYUN CHANG ◽

LIANG YIN ◽

JUN LI ◽

TING ZHOU ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus ◽

Methylation Status

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The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus

Clinical Epigenetics ◽

10.1186/s13148-020-00896-4 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Sanabil Ali Hassan Ahmed ◽

Suraiya Anjum Ansari ◽

Eric P. K. Mensah-Brown ◽

Bright Starling Emerald

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus

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The Association between Genomic DNA Methylation and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2019/2494057 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Hong-Hong Zhang ◽

Xingfa Han ◽

Mengmeng Wang ◽

Qingfang Hu ◽

Sicheng Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Dna Methylation ◽

Type 2 Diabetes Mellitus ◽

Peripheral Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Genomic Dna ◽

Stepwise Regression ◽

Multiple Stepwise Regression Analysis

Aim. DNA methylation is thought to be involved in regulating the expression of key genes and inducing diabetic peripheral neuropathy (DPN). However, clinically, the level of whole-genome DNA methylation and its relationship with DPN remains unclear. Methods. 186 patients with type 2 diabetes mellitus (T2DM) admitted to the Second Affiliated Hospital of Soochow University since Jul. 2016 to Oct. 2017 were enrolled in the study, including 100 patients in the DPN group and 86 patients in the non-DPN group, diagnosed with Toronto Clinical Scoring System (TCSS). Clinical and biochemical characteristics between the two groups were compared, and the correlations with TCSS scores were analyzed. Furthermore, the levels of genomic DNA methylation of leukocytes, measured with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), were also analyzed between the two groups. Results. Age, duration, triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), creatinine, uric acid (UA), blood urea nitrogen (BUN), and C-reactive protein (CRP) were significantly higher in the DPN group. Estimated glomerular filtration rate (eGFR) and the level of genomic DNA methylation were much lower in the DPN group. Spearman correlation analysis showed that TCSS was positively correlated with age, duration, UA, and CRP and was negatively correlated with body mass index (BMI), eGFR, and the level of genomic DNA methylation. Interestingly, multiple stepwise regression analysis showed that only duration, genomic DNA methylation, and eGFR had impacts on TCSS. The results also showed that the levels of genomic DNA methylation did not change significantly whether or not there was renal injury. Another multiple stepwise regression analysis showed that TCSS and BMI were the influencing factors of genomic DNA methylation. Finally, we found that genomic DNA methylation levels were decreased significantly in the DPN group compared with the non-DPN group when the duration is ≥5 years or BMI≥25 kg/m2. Conclusion. Low level of genomic DNA methylation is a relative specific risk factor of diabetic peripheral neuropathy in patients with type 2 diabetes.

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