ToF-SIMS revealing sphingolipids composition in extracellular vesicles and paternal β-cells after persistent...

Extended periods of hyperglycemia (HG) can lead to dysfunction and metabolic disorders of sphingolipids (SPs) and their subsequent accumulation in cells. It can trigger a range of complications, including kidney and neurodegenerative diseases. We compared the levels of selected ceramides (CER), hexosylceramides (HexCER), and glycosphingolipids (GSLs) in potential HG biomarkers - extracellular vesicles (EVs). These EVs were derived in vitro from human β-cells cultured under different glucose conditions. We utilized Time of Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) for SPs analysis and found that the lipid profiles differ between large and small EVs, with some SP lipids being more enriched in EVs compared to cells. Interestingly, our study revealed that HG only regulates the lipid content from the GSLs group to normoglycemia. Collectively, our findings underscore the potential applications of ToF-SIMS in characterizing the impact of different culture conditions on lipid levels. As far as we know, our study is the first which employs ToF-SIMS in analyzing the effects of HG on SP levels in EVs and their parental β-cells.