Ganglioside Contributes to Regulation of Insulin Resistance in Human Aortic Endothelial Cells after TNFα Stimulation

Vascular insulin resistance induced by inflammatory cytokines leads to the initiation and development of vascular diseases. In humans, circulating TNFα levels are increased in aging, but the correlation between vascular insulin resistance and plasma TNFα levels is said to be relatively weak. Currently, the precise molecular mechanisms of vascular insulin resistance mediated by TNFα are not well characterized. It has been demonstrated that gangliosides (molecules composed of glycosphingolipids with one or more sialic acids) are fine regulators of insulin signaling and that changed cell surface gangliosides compositions in physio-pathological conditions result in altered cellular responses. Previously, we demonstrated that increased ganglioside GM1 with senescence and aging contributes to insulin resistance in endothelial cells (ECs)¹. Thus, gangliosides are considered to play important roles in insulin resistance. We aimed at clarifying whether gangliosides contribute to vascular insulin resistance after inflammatory stimulation. In this study, we used human aortic ECs and examined expression levels of gangliosides after treatment with different concentrations of TNFα for different time intervals for mimicking in vivo acute or chronic inflammatory situations. And also, we examined insulin signaling and related-molecules by immunoblotting after TNFα treatment with or without inhibitor of ganglioside synthesis. In this congress, we will show and discuss about relationship between insulin resistance and ganglioside expression in TNFα-stimulated ECs.

1: Sasaki N, Itakura Y, Toyoda M. Ganglioside GM1 Contributes to the State of Insulin Resistance in Senescent Human Arterial Endothelial Cells. J Biol Chem. 2015; 290:25475–25486.