Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and β-Cell Dysfunction

Figure 1

Insulin resistance and the role of inflammation. Overnutrition leads to high levels of lipids and glucose and overtime development of obesity and metabolic syndrome (MetS), ultimately causing chronic low-grade inflammation. High nutrients can modulate insulin resistance by altering the insulin-signalling cascade through changes in IRS1, PI3K, and AKT phosphorylation. High lipids can also promote inflammation through generation of ceramide, and high glucose increases overall oxidative stress. During T2DM progression the insulin resistant tissues promote the exhaustion of insulin secreting β-cells, which activates defensive mechanisms leading to lower insulin release.