Permethrin decreased insulin secretion and the expression of proteins linked to metabolism and exocytosis in INS832/3 pancreatic beta cells

Permethrin, a widely used pyrethroid insecticide, has been suspected of contributing to metabolic disturbances, insulin resistance, and diabetes, but its effect on pancreatic beta cells has never been investigated. We evaluated the impact of one-week exposure to sublethal concentrations (1 μM and 10 μM) of permethrin on the function and viability of INS832/3 pancreatic beta cells. Permethrin significantly decreased glucose- and KCl-stimulated insulin secretion despite only a partial reduction in intracellular insulin levels. It also altered the expression of proteins involved in glucose metabolism, energy sensing, lipid storage and exocytosis machinery, suggesting a multifaceted impairment of cell functioning. A comparative analysis using HepG2 liver cells revealed tissue-specific responses. This is the first report showing that permethrin exposure decreases insulin secretion by pancreatic beta cells. This data can help to better evaluate the risk assessment of permethrin as a potential endocrine disruptor that may increase the risk of diabetes. • Permethrin decreases insulin secretion in INS832/3 pancreatic beta-cells • AMPK phosphorylation is reduced by sublethal permethrin exposure • Beta-cell metabolic enzymes are downregulated by permethrin • HepG2 cells show opposite AMPK and ATP-CL response to permethrin • Permethrin disrupts insulin secretion without causing ER or oxidative stress