Insulin resistance, endothelial and adipose dysfunction and atherosclerosis

Abstract

Diabetes mellitus is a multisystem group of disorders associated with insulin resistance, metabolic stress, endothelial and adipose dysfunction and accelerated atherosclerosis. As the different players leading to atherosclerosis are known, the pathogenesis and eventually targets for treatment can be identified. The purpose of this review is to update the newer aspects of pathogenic factors as well as newer putative biomarkers in atherosclerosis. Hyperglycemia causes beta cell dysfunction, which results in impaired insulin secretion, endoplasmic reticulum stress and overproduction of reactive oxygen species. Lipotoxicity, or the accumulation of increased amounts of lipids in non-adipose tissue is found in the insulin producing pancreatic beta cells impairing their function. Gluco-lipotoxicity leads to the production of inflammatory cytokines, which damage the vasculature. Endothelial dysfunction, which occurs due to all these insults can be studied by biochemical alterations and by non-invasive imaging techniques. In addition, epigenetic changes have been identified in the pathogenesis. More recent biomediators were identified to be involved in the process of atherogenesis including adiponectin, leptin, resistin, adropin, visfatin, hepatokines, bone morphogenetic protein, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), families of micro RNAs, extracellular vesicles (exosomes, ectosomes) and a variety of environmental factors. In view of managing conventional risk factors has not prevented atherosclerotic complications, the better understanding the role of pro- and anti- atherogenic factors may allow the development of novel drugs to modify them.