Metabolomic identification of biochemical changes induced by fluoxetine in an insulinoma cell line (MIN6)

BACKGROUND AND PURPOSE: The use of fluoxetine raises the risk of pancreatic beta-cell dysfunction. However, the specific mechanism behind its mechanism of action in beta cells is unknown. This study investigated the cellular response of MIN6 cells to fluoxetine using untargeted cell-based metabolomics. EXPERIMENTAL APPROACH: Metabolic profiling of MIN6 cells was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. FINDINGS/RESULTS: Sixty-six metabolites that had been differentially expressed between the control and fluoxetine-treated groups demonstrated that the citric acid cycle is mainly perturbed by fluoxetine treatment. CONCLUSION AND IMPLICATIONS: The current study provides insights into the molecular mechanisms of fluoxetine effects in MIN6 cells.