The role of DNA methylation in the pathogenesis of type 2 diabetes mellitus

Abstract

Diabetes mellitus (DM) is a chronic condition characterised by β cell dysfunction and persistent hyperglycaemia. The disorder can be due to the absence of adequate pancreatic insulin production or a weak cellular response to insulin signalling. Among the three types of DM, namely, type 1 DM (T1DM), type 2 DM (T2DM), and gestational DM (GDM); T2DM accounts for almost 90% of diabetes cases worldwide.Epigenetic traits are stably heritable phenotypes that result from certain changes that affect gene function without altering the gene sequence. While epigenetic traits are considered reversible modifications, they can be inherited mitotically and meiotically. In addition, epigenetic traits can randomly arise in response to environmental factors or certain genetic mutations or lesions, such as those affecting the enzymes that catalyse the epigenetic modification. In this review, we focus on the role of DNA methylation, a type of epigenetic modification, in the pathogenesis of T2DM.

Keywords: DNA methylation; Diabetes mellitus; Hypermethylation; Hypomethylation; Type 2 diabetes mellitus.

Fig. 1

Worldwide DM statistics in 2019 for the age group 20–79 years old and the projections for years 2030 and 2045

Fig. 2

The epigenetic pathway and the three categories of signals proposed. The extracellular epigenator signal triggers the initiation of the epigenetic pathway. The epigenetic initiator receives the signal from the epigenator and determines the chromatin state for establishing the epigenetic pathway. The epigenetic maintainer sustains the chromatin state in succeeding generations