Figure 1. Possible mechanisms through which insulin resistance in ECs, SMCs, and macrophages promotes atherogenesis.
In early-mid-stage atherosclerotic lesions, insulin resistance is associated with a decrease in eNOS activation and NO production and increase in VCAM-1 expression by arterial ECs. Both of these perturbations may be due to down-regulation of the insulin receptor-Akt1 pathway in ECs. The net effect is endothelial dysfunction and activation, leading to defective vasodilation and increased entry of inflammatory cells into the plaque. Inset, summary scheme of canonical insulin receptor signaling pathway; see text for details.