DNA methylation and its role in the pathogenesis of diabetes

Abstract

Although the factors responsible for the recent increase in the prevalence of diabetes worldwide are not entirely known, the morbidity associated with this disease results in substantial health and economic burden on society. Epigenetic modifications, including DNA methylation have been identified as one mechanism by which the environment interacts with the genome and there is evidence that alterations in DNA methylation may contribute to the increased prevalence of both Type 1 and Type 2 diabetes. This review provides a summary of DNA methylation and its role in gene regulation, and includes descriptions of various techniques to measure site-specific and genome wide DNA methylation changes. In addition, we review current literature highlighting the complex relationship between DNA methylation, gene expression, and the development of diabetes and related complications. In studies where both DNA methylation and gene expression changes were reported, DNA methylation status had a strong inverse correlation with gene expression, suggesting that this interaction may be a potential future therapeutic target. We highlight the emerging use of genome wide DNA methylation profiles as a biomarker to predict patients at risk of developing diabetes or specific complications of diabetes. Developing a predictive model that incorporates both genetic information and DNA methylation changes may be an effective diagnostic approach for all types of diabetes and could lead to additional innovative therapies.

Increased Expression of miR-483-3p Impairs the Vascular Response to Injury in Type 2 Diabetes

“…In a subsequent study (40), the same group identified VEZF1 to bind to CpG islands, thereby protecting them from de novo DNA methylation. These findings are in line with observations of aberrant DNA methylation being involved in the pathogenesis of type 1 diabetes and T2D (41), which is assumed to play a role in phenomena like the higher frequency of T2D in children born to mothers suffering from malnutrition during pregnancy (42). Interestingly, miR-483-3p expression in adipose tissue of low-birth weight adult humans and in prediabetic adult rats that had been exposed to suboptimal nutrition in early life was elevated, thus suggesting an epigenetic priming by nutrition in early life (17).…”

Exposure to PM2.5 during pregnancy or lactation increases methylation while reducing the expression of Pdx1 and NEUROG3 in mouse pancreatic islets

“…Considering that DNA methylation is critical for processes such as embryonic development of mammals, tissue-specific gene expression regulation and genomic imprinting [17], it may suggest that exposure to air pollution during pregnancy and lactation methylated the aforementioned genes, passing such genomic imprinting on to following generations.…”

“…Insulin secretion deficiency underlies the transition from normoglycemia to hyperglycemia in type 1 and type 2 diabetes alike [17]. Though it is known that circulating insulin originates almost exclusively from β cells located in pancreatic islets, our comprehension about the molecular mechanisms responsible for regulating β-cell function in healthy and diseased mammals alike remain incomplete.…”

Eicosapentaenoic acid induces DNA demethylation in carcinoma cells through a TET1‐dependent mechanism

“…Besides EPA, a-linolenic acid, and docosahexaenoic acid, the other well-known n-3 PUFAs were reported to exert beneficial effects on cancer cells and in chronic diseases, such as insulin resistance and cardiovascular disease (50,51), which are strongly related to abnormal DNA methylation (52,53). If individual n-3 PUFAs, which are used generally as a mixture, exhibit the same epigenetic action as EPA, then they may also act as demethylating agents.…”