ReviewGlycemic memory associated epigenetic changes
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Glycemic variability and diabetic complications
Cardiovascular complications remain the major cause of morbidity and mortality in the diabetic population [1]. Patients with type 1 or type 2 diabetes have a two- to four-fold higher risk of cardiovascular disease when compared to healthy individuals [2], [3], and those with impaired glucose tolerance alone have a cardiovascular disease risk comparable to type 2 diabetics [4]. It is increasingly appreciated that exposure to high glucose is the major factor leading to these complications.
Studying epigenetic changes
Epigenetics describes the study of heritable changes in gene activity and expression independent of changes in nucleotide sequence [16]. These epigenetic changes are potentially reversible and modulated by the environment, diet or pharmacological intervention (Fig. 2). This in turn can mediate changes in genomic stability and gene expression [17], [18], [19]. Essentially the field of epigenetics provides a link between genotype and phenotype, which can help explain how cells carrying identical
Nutritional intervention and epigenetic modifications
Many studies have examined links between obesity, energy metabolism, nutrient balance and epigenetic modifications [34], [35], [36], [37], [38]. Obesity is associated with loss of function of the histone demethylase, Jhdm2a, resulting in decreased expression of the metabolically active gene peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in skeletal muscle and impaired uncoupling protein 1 expression in brown adipose tissue suggesting a relationship between epigenetic mechanisms
Epigenetic regulation of diabetic complications
Oxidative stress, dyslipidemia and hyperglycemia are thought to be associated with the development of diabetic complications. The major event in the progression of diabetic complications is vascular inflammation, triggered by a pathway of mediators to enhance inflammatory signalling. Nuclear factor-κB (NFκB) is one of the predominant transcription factors that are activated under diabetic conditions in the inflammatory pathway, leading to recruitment of monocytes and macrophages to the vessel
The role of histone-modifying enzymes in glycemic variability
Currently there is intensive research into the identification and characterisation of the enzymes that control and direct histone modifications [54], [55], of which the methyltransferases are most specific. Lysine methyltransferases have enormous specificity compared to acetyltransferases, usually modifying one single lysine on the histone tail [17], [56]. The existence of lysine demethylases remained contentious for many years following the discovery of histone methyltransferases (HMTase). The
The current landscape and perspectives—where to next?
Investigators in our laboratory are interested in examining the dynamic state of epigenetic changes in response to environmental stimuli. Specifically, hyperglycemia and the persistence of epigenetic phenomena are a primary focus of some of the research currently investigated. In fact, many researchers are attempting to unravel the molecular determinants associated with recognizing the chromatin template and regulate the histone code. Understanding the exact changes in histone methylation, the
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2021, Medical EpigeneticsAdenosine kinase and cardiovascular fetal programming in gestational diabetes mellitus
2020, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :Noteworthy, the alterations described can be found in the fetoplacental vasculature from GDM pregnancies even after achieving optimal glycaemia by following restricted diet or insulin treatment, i.e. insulin therapy [3,18,71]. Thus, cell programming possible triggered by the exposure to high d-glucose is likely [72,73]. The increased extracellular concentration of adenosine resulting from lower hENT1 activity results in activation of the four-member family of adenosine receptors, i.e. A1 adenosine receptors (A1AR), A2AAR, A2BAR, and A3AR [20,74–76].