Epigenetic Modifications Associated with the Pathogenesis of Type 2 Diabetes Mellitus.

ABSTRACT

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder. Pancreatic ß-cell dysfunction and insulin resistance are the most common and crucial events of T2DM. Increasing evidence suggests the association of epigenetic modifications with the pathogenesis of T2DM through the changes in important biological processes including pancreatic ß- cell differentiation, development and maintenance of normal ß-cell function. Insulin sensitivity by the peripheral glucose uptake tissues is also changed by the altered epigenetic mechanisms. In this review, we discussed the major epigenetic alterations and their effects on ß-cell function, insulin secretion and insulin resistance in context of T2DM. METHODS: We investigated the presently available epigenetic modifications including DNA methylation, posttranslational histone modifications, ATP-dependent chromatin remodeling and non-coding RNAs related to the pathogenesis of T2DM. Published literatures on this topic were searched both on Google Scholar and Pubmed with related keywords and investigated for relevant information. RESULTS: The epigenetic modifications introduce changes in gene expression which are essential for appropriate ß-cell development and functions, insulin secretion and sensitivity resulting in the pathogenesis of T2DM. Interestingly, T2DM could also be a prominent reason for the mentioned epigenetic alterations. CONCLUSION: This review article emphasized on the epigenetic modifications associated with T2DM and discussed the consequences in deterioration of the disease condition.