Title:Insights into the Role of DNA Methylation and Protein Misfolding in Diabetes Mellitus
Volume: 19
Issue: 6
Author(s): Sara M. Ahmed, Dina Johar, Mohamed Medhat Ali and Nagwa El-Badri*
Affiliation:
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza,Egypt
Keywords:
Diabetes, DNA methylation, protein folding, diet, aging, obesity.
Abstract:
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.
