Abstract
Significance: A strong relationship between hyperglycemia, impaired insulin pathway, and cardiovascular disease in type 2 diabetes (T2D) is linked to oxidative stress and inflammation. Immunometabolic pathways link these pathogenic processes and pose important potential therapeutic targets.Recent Advances: The link between immunity and metabolism is bidirectional and includes the role of inflammation in the pathogenesis of metabolic disorders such as T2D, obesity, metabolic syndrome, and hypertension and the role of metabolic factors in regulation of immune cell functions. Low-grade inflammation, oxidative stress, balance between superoxide and nitric oxide, and the infiltration of macrophages, T cells, and B cells in insulin-sensitive tissues lead to metabolic impairment and accelerated aging.Critical Issues: Inflammatory infiltrate and altered immune cell phenotype precede development of metabolic disorders. Inflammatory changes are tightly linked to alterations in metabolic status and energy expenditure and are controlled by epigenetic mechanisms.Future Directions: A better comprehension of these mechanistic insights is of utmost importance to identify novel molecular targets. In this study, we describe a complex scenario of epigenetic changes and immunometabolism linking to diabetes and aging-associated vascular disease. Antioxid. Redox Signal. 29, 257–274.
Highlights
The prevalence of obesity and type 2 diabetes (T2D) mellitus is alarmingly increasing worldwide [12, 71]
We have shown that diabetes induces a profound alteration of miRNA expression in the heart and, most importantly, these detrimental signatures are not reverted by glycemic control [24]
We have recently studied the role of mitochondrial adaptor p66Shc in reactive oxygen species (ROS)-driven insulin resistance in the endothelial cells (ECs). p66Shc silencing in vivo restored endothelial function through modulation of the insulin receptor substrate (IRS)-1/AKT/endothelial nitric oxide synthase (eNOS) [120]
Summary
The prevalence of obesity and type 2 diabetes (T2D) mellitus is alarmingly increasing worldwide [12, 71]. Immune cell infiltration is a key feature linking obesity to diabetes, as proinflammatory cytokines, macrophages, and T cells are essential for the development of insulin resistance [110]. In the setting of diabetes, promoter hypomethylation leads to increased expression of genes involved in inflammation, adiposity, b cell dysfunction, and vascular damage [88].
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