The Contribution of Singlet Oxygen to Insulin Resistance

Oxidative Medicine and Cellular Longevity
Arnold N Onyango

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-in...Continue Reading

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Citations

Dec 14, 2017·Lipids in Health and Disease·Mohamed Raâfet Ben KhedherMohamed Hammami
Mar 28, 2019·Journal of Cellular Physiology·Tahereh FarkhondehBabak Roshanravan
Aug 18, 2018·Oxidative Medicine and Cellular Longevity·Arnold N Onyango
Feb 3, 2022·Expert Opinion on Therapeutic Targets·Aizhen ZhaoYe Tian

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