Despite the fact that environmental pollution has been implicated in the global rise of diabetes, the research on the impact of emerging pollutants such as novel flame retardants remains limited. In line with the shift towards the use of non-animal approaches in toxicological testing, this study aimed to investigate the effects of two novel flame retardants tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPhP) in rat (INS1E) and human (NES2Y) pancreatic beta-cell lines. One-week exposure to 1 μM and 10 μM TDCIPP and TPhP altered intracellular insulin and proinsulin levels, but not the levels of secreted insulin (despite the presence of a statistically insignificant trend). The exposures also altered the protein expression of several factors involved in beta-cell metabolic pathways and signaling, including ATP citrate lyase, isocitrate dehydrogenase 1, perilipins, glucose transporters, ER stress-related factors, and antioxidant enzymes. This study has brought new and valuable insights into the toxicity of TDCIPP and TPhP on beta-cell function and revealed alterations that might impact insulin secretion after more extended exposure. It also adds to the scarce studies using in vitro pancreatic beta-cells models in toxicological testing, thereby promoting the development of non-animal testing strategy for identifying pro-diabetic effects of chemical pollutants.

• Keywords
• Beta-cells, Diabetes, Insulin, Metabolic disease, TDCIPP, TPhP,
• MeSH
• Insulin-Secreting Cells * drug effects   metabolism   MeSH
• Cell Line MeSH
• Homeostasis * drug effects   MeSH
• Insulin * metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Organophosphates toxicity   MeSH
• Organophosphorus Compounds * toxicity   MeSH
• Proinsulin metabolism   MeSH
• Flame Retardants * toxicity   MeSH
• Insulin Secretion drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Insulin * MeSH
• Organophosphates MeSH
• Organophosphorus Compounds * MeSH
• Proinsulin MeSH
• Flame Retardants * MeSH
• triphenyl phosphate MeSH Browser
• tris(1,3-dichloro-2-propyl)phosphate MeSH Browser