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Table 1 DNA methylation alterations in T2DM

From: DNA methylation landscapes in the pathogenesis of type 2 diabetes mellitus

Genes/Susceptibility factors Methylated status Insulin-sensitive organs Effects References
PPARGC1A Hypermethylation Human pancreatic islets Influenced glucose-stimulated insulin secretion [17]
KCNQ1 Hypermethylation Human pancreatic islets Increased the risk of T2DM [20]
Insulin gene Demethylation Human and mouse islet cell Inhibited the function of beta cell [21]
Insulin gene Hypermethylation Human pancreatic islets Increased the levels of HbA1c [22]
PDX-1 Hypermethylation Human pancreatic islets Associated with the insulin secretion [23]
GLP1R Hypermethylation Human pancreatic islets Positively associated with BMI and HbA1c [24]
MEG3-DLK1 microRNA Hypermethylation Human pancreatic islets Caused the increase of β cell apoptosis [25]
Ageing Hypermethylation Rat pancreatic islets Associated with molecular inflammation [26]
NDUFB6 Hypermethylation Human skeletal muscle Influenced insulin sensitivity [35]
COX5a Hypermethylation Rat skeletal muscle Associated with mitochondrial dysfunction [36]
COX7A1 Hypermethylation Human skeletal muscle Associated with glucose uptake in vivo [37]
Gastric bypass surgery Hypomethylation Human skeletal muscle Remodeled the promoter methylation of PGC-1α and PDK4 [38]
Acute exercise Hypomethylation Human skeletal muscle Activated contraction-induced gene [39]
Ionizing radiation Hypermethylation Mice skeletal muscle cells Increased the risk of insulin resistance [40]
Insulin and glucose exposure Hypermethylation and hypomethylation Human skeletal muscle Altered the DAPK3 methylation [41]
Gck Hypermethylation Rat liver Involved in the development of insulin resistance [42, 43]
TNFα Hypermethylation Mice liver and adipose tissue Associated with the reduction of inflammation [44]
Metformin transporter genes Demethylation Human liver Improved hyperglycaemia and obesity [45]
In-utero malnutrition Hypermethylation Mice liver Influenced the expression of lipogenic genes [46]
Loss of MBD2 Hypermethylation Mice liver Protected mice from insulin resistance [52]
IGFBP1 and IGFBP7 Hypermethylation Human peripheral blood Associated with insulin resistance [53, 54]
Alu repeats Hypermethylation Human peripheral blood leukocytes Associated with insulin resistance [59]
LINE-1 Hypomethylation Human peripheral blood Increased the risk of metabolic worsening [60]
MCP-1 Hypomethylation Human peripheral blood Increased the serum MCP-1 level [61]
TCF7L2 Hypermethylation Human peripheral blood Positively associated with fasting glucose [62]
TXNIP Hypomethylation Human peripheral blood Increased HbA1c and fasting glucose [65]
NR4A1 Hypomethylation Human peripheral blood Decreased the blood glucose [66]
Aging Hypermethylation Human brain and blood Remodeled DNA methylation [67]