Metabolomic insights into rotenone-induced dysregulation of purine metabolism and impaired insulin secretion in murine pancreatic beta cells

Abstract

Rotenone, an insecticide, and herbicide has been associated with various environmental and health concerns. This study investigates the molecular alterations in rotenone-treated murine pancreatic beta cells, using untargeted metabolomics based on liquid chromatography-mass spectrometry. We established a model mimicking rotenone toxicity in MIN6 cells and observed decreased insulin secretion despite no significant loss of cellular viability. Our untargeted metabolomics analysis revealed a decrease in 19 metabolites and an increase in 62 metabolites following exposure to rotenone. Mapping these changes onto metabolic pathways, we found that purine metabolism underwent significant alterations. Critical metabolites in this pathway, including adenine, adenosine monophosphate, guanine, and others, exhibited a substantial increase upon rotenone treatment. This study underscores the utility of untargeted metabolomics for investigating molecular alterations due to rotenone exposure. It further highlights rotenone’s significant impact on purine metabolism, providing potential insights into the mechanisms of rotenone-associated diabetes risk.