Insights into the Role of DNA Methylation and Protein Misfolding in Diabetes Mellitus

Background: Diabetes mellitus is a metabolic disorder that is characterized by impaired glucose tolerance resulting from defects in insulin secretion, insulin action, or both. Epigenetic modifications, which are defined as inherited changes in gene expression that occur without changes in gene sequence, are involved in the etiology of diabetes. Methods: In this review, we focused on the role of DNA methylation and protein misfolding and their contribution to the development of both type 1 and type 2 diabetes mellitus. Results: Changes in DNA methylation in particular are highly associated with the development of diabetes. Protein function is dependent on their proper folding in the endoplasmic reticulum. Defective protein folding and consequently their functions have also been reported to play a role. Early treatment of diabetes has proven to be of great benefit, as even transient hyperglycemia may lead to pathological effects and complications later on. This has been explained by the theory of the development of a metabolic memory in diabetes. The basis for this metabolic memory was attributed to oxidative stress, chronic inflammation, non-enzymatic glycation of proteins and importantly, epigenetic changes. This highlights the importance of linking new therapeutics targeting epigenetic mechanisms with traditional antidiabetic drugs. Conclusion: Although new data is evolving on the relation between DNA methylation, protein misfolding, and the etiology of diabetes, more studies are required for developing new relevant diagnostics and therapeutics.