Vascular
insulin resistance induced by inflammatory
cytokines leads to the initiation and development of
vascular diseases. In humans, circulating TNFα levels are increased during aging, suggesting a correlation between vascular
insulin resistance and plasma TNFα levels. Currently, the precise molecular mechanisms of vascular
insulin resistance mediated by TNFα are not well characterized. We aimed at clarifying whether
glycosphingolipids contribute to vascular
insulin resistance after inflammatory stimulation. In this study, we examined vascular
insulin resistance using human aortic endothelial cells
after treatment with different concentrations of TNFα for different time intervals for mimicking in vivo acute or chronic inflammatory situations. We show that
ganglioside GM1 levels on cell membranes change depending on time of exposure to TNFα and its concentration and that the GM1 expression is associated with specific extracellular/intracellular regulation of the
insulin signaling cascade. Furthermore, we provide evidence that factors such as aging and senescence affect the regulation of
insulin resistance. Our data suggest that GM1 is a key player in the induction of vascular
insulin resistance after short- or long-term exposure to TNFα and is a good extracellular target for prevention and cure of
vascular diseases.