The Contribution of Singlet Oxygen to Insulin Resistance

Figure 1

TLR4-dependent pathways for the development of insulin resistance via (i) the activation of serine kinases such as PKC isoforms, IKK, JNK, and p38 MAPK that induce serine phosphorylation of insulin receptor substrate (IRS) and (ii) the formation of reactive oxygen and nitrogen species such as hydrogen peroxide (H₂O₂), nitric oxide (NO), peroxynitrite (ONOO−), and singlet oxygen (¹O₂). Enteric lipopolysaccharide (LPS) is a direct ligand of TLR4, while fatty acids and sugars such as fructose activate this pathway via DAG, PKC, and Nox-derived ROS.