Ganglioside GM1 contributes to extracellular/intracellular regulation of insulin resistance, impairment of insulin signaling and down-stream eNOS activation, in human aortic endothelial cells after short- or long-term exposure to TNFα

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Norihiko SasakiMasashi Toyoda

Abstract

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 mimickingin vivoacute 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...Continue Reading

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Citations

Apr 25, 2019·International Journal of Molecular Sciences·Norihiko SasakiMasashi Toyoda
Dec 22, 2019·International Journal of Molecular Sciences·Norihiko Sasaki, Masashi Toyoda
Nov 19, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Shuwen YueXing Wang

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Methods Mentioned

BETA
fluorescence-activated cell sorting
PCR
flow cytometry
FACS

Software Mentioned

ImageJ

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