The Contribution of Singlet Oxygen to Insulin Resistance

Abstract

Insulin resistance contributes to the development of diabetes and cardiovascular dysfunctions. Recent studies showed that elevated singlet oxygen-mediated lipid peroxidation precedes and predicts diet-induced insulin resistance (IR), and neutrophils were suggested to be responsible for such singlet oxygen production. This review highlights literature suggesting that insulin-responsive cells such as endothelial cells, hepatocytes, adipocytes, and myocytes also produce singlet oxygen, which contributes to insulin resistance, for example, by generating bioactive aldehydes, inducing endoplasmic reticulum (ER) stress, and modifying mitochondrial DNA. In these cells, nutrient overload leads to the activation of Toll-like receptor 4 and other receptors, leading to the production of both peroxynitrite and hydrogen peroxide, which react to produce singlet oxygen. Cytochrome P450 2E1 and cytochrome c also contribute to singlet oxygen formation in the ER and mitochondria, respectively. Endothelial cell-derived singlet oxygen is suggested to mediate the formation of oxidized low-density lipoprotein which perpetuates IR, partly through neutrophil recruitment to adipose tissue. New singlet oxygen-involving pathways for the formation of IR-inducing bioactive aldehydes such as 4-hydroperoxy-(or hydroxy or oxo)-2-nonenal, malondialdehyde, and cholesterol secosterol A are proposed. Strategies against IR should target the singlet oxygen-producing pathways, singlet oxygen quenching, and singlet oxygen-induced cellular responses.

Mechanisms of titanium dioxide nanoparticle‐induced oxidative stress and modulation of plasma glucose in mice

“…IR is a major contributory mechanism for diabetes . During the postprandial state, insulin secretion from pancreatic β‐cells controls systemic plasma glucose homeostasis by promoting anabolic processes in liver cells . Previous reports have shown that phosphorylation of IRS1 at Ser 307, which antagonizes Akt‐ser 473 phosphorylation, leads to IR and increased plasma glucose .…”

“…17 During the postprandial state, insulin secretion from pancreatic β-cells controls systemic plasma glucose homeostasis by promoting anabolic processes in liver cells. 17,18 Previous reports have shown that phosphorylation of IRS1 at Ser 307, which antagonizes Akt-ser 473 phosphorylation, leads to IR and increased plasma glucose. 19,20 In our experiments, Res relieved ER stress and ROS generation and CYP enzymes expressed throughout the human body play a crucial role in human physiology and are involved in drug and xenobiotic metabolism as well as biosynthesis of endogenous molecules.…”

Impact of chrysin on the molecular mechanisms underlying diabetic complications

“…Chrysin ( (Onyango, 2017;Sarangi et al, 2012). The inactivation of RAGE ameliorates the myocardial ischemic and progression of atherosclerosis in the diabetic patients (Suchal et al, 2017;Yamagishi & Matsui, 2018).…”

Carbohydrate metabolism disorders in women in procreative age

“…insulin resistance -IR) -oznacza zmniejszoną wrażliwość tkanek na działanie insuliny, często powodującą pojawienie się innych zaburzeń w gospodarce węglowodanowej. 17…”