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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 8765972, 14 pages
https://doi.org/10.1155/2017/8765972
Review Article

The Contribution of Singlet Oxygen to Insulin Resistance

Department of Food Science and Technology, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000, Nairobi 00200, Kenya

Correspondence should be addressed to Arnold N. Onyango; ek.ca.taukj@ognayno.dlonra

Received 24 April 2017; Accepted 7 August 2017; Published 7 September 2017

Academic Editor: Victor M. Victor

Copyright © 2017 Arnold N. Onyango. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.