The role of inflammation in vascular insulin resistance with focus on IL-6

The present review focuses on the possible role of interleukin-(IL)-6 in vascular insulin resistance. The endothelium plays an important role in regulating the tone of the vasculature by releasing nitric oxide (NO) to the smooth muscles of the vessels, thereby regulating the distribution of blood flow to the various tissues in relation to their energy demand. A dysfunctioning endothelium has been associated with both initiation and progression of atherosclerotic cardiovascular (CV) disease and has been shown to predate the onset of hyperglycemia in the natural history of type 2 diabetes. It is likely that chronic low-level inflammation plays an important role in developing endothelial dysfunction mainly through proinflammatory actions of tumor necrosis factor alpha (TNF-alpha). TNF-alpha induces production of IL-6 and it has been suggested that a causal relationship exists between endothelial dysfunction and these cytokines. With regard to vascular insulin resistance, the available data point to a direct pathogenic role of TNF-alpha in mediating endothelial dysfunction, whereas with regard to IL-6 evidence is sparse and does not allow any firm conclusions.