Polystyrene nanoparticles strengthen high glucose toxicity associated with alteration in insulin signaling pathway in...

Using Caenorhabditis elegans as animal model, we investigated the effect of exposure to polystyrene nanoparticles (PS-NPs) in the range of μg/L on high glucose toxicity induction. With lifespan and locomotion behavior as endpoints, we observed that PS-NP (10 and 100 μg/L) enhanced toxicity in 50 mM glucose treated animals. In insulin signaling pathway, expressions of genes encoding insulin receptor (daf-2), kinases (age-1 and akt-1/2), and insulin peptides (ins-9, ins-6, and daf-28) were increased, and expressions of daf-16 and its target of sod-3 were decreased in high glucose treated nematodes followed by PS-NP exposure. Toxicity enhancement in high glucose treated nematodes by PS-NP exposure was inhibited by RNAi of daf-2, age-1, akt-2, akt-1, and 3 insulin peptides genes, but increased by RNAi of daf-16 and sod-3. The resistance of animals with RNAi of daf-2 to toxicity in high glucose treated nematodes followed by PS-NP exposure could be suppressed by RNAi of daf-16. Moreover, in high glucose treated animals followed by PS-NP exposure, daf-2 expression was inhibited by RNAi of ins-6, ins-9, and daf-28. Our data demonstrated the risk of PS-NP exposure in enhancing the high glucose toxicity. More importantly, alteration in expression of genes in insulin signaling pathway was associated with the toxicity enhancement in high glucose treated nematodes followed by PS-NP exposure.