Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Abstract

Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

Evaluation of Pancreatic and Extra Pancreatic Effects of Branched Amino Acids

“…The results show significant restoration of the secretory function under the influence of BCAA. Multiple mechanisms have been suggested through which chronic hyperglycemia and hyperlipidemia may impair beta cell function [22] including: prolonged exposure to increased glucose concentrations causing gradual loss of insulin gene expression [23], the high demand on ER for the synthesis of proinsulin leading to cellular stress [24], increases the metabolic flux into the mitochondria and accumulation of intermediates of lipid metabolism induce excessive generation of ROS which leads to chronic oxidative stress and eventually to inflammatory response that trigger apoptosis by initiating pro inflammatory signal [25]. Therefore, we suggest that these acids could have antioxidant ability or not, which could be the reason for restoring the secretory function of the pancreatic β-cell under the effect of glucotoxicty and lipotoxicty.…”

DNA methylation profile of genes related to immune response in generalized periodontitis

“…Cytokine production may be influenced not only by genetic factors but also by epigenetic ones. Interestingly, epigenetic events are related to the development of diseases with inflammatory profile . Epigenetics comprises the alterations in patterns of gene expression, which do not involve changes in the DNA sequence .…”

Early targeted DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in different stages of impaired glucose homeostasis Cardiovascular Diabetology

“…In order to obtain a better understanding of the mechanisms underlying progress of Pre-Diab toward T2D and CV complications, we studied some of the epigenetic modifications that can occur named DNA methylation [7]. Clinical evidence reported that peripheral insulin resistance, hyperglycemia and inflammation can significantly alter DNA methylation in early stages by providing a putative mechanistic link between glucose homeostasis imbalance, and vascular damage [8][9][10][11][12][13][14][15]. DNA methylation mainly occurs at cytosine bases located both in gene promoter and "CpG islands", which represent large regions with high frequency (about 50%) of cytosine-phosphate-guanine (CpG) dinucleotides [7,16,17].…”