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Metabolomic identification of biochemical changes induced by fluoxetine in an insulinoma cell line (MIN6)
Surachai Ngamratanapaiboon1, Krittaboon Pornchokchai2, Siriphattarinya Wongpitoonmanachai2
1Division of Pharmacology, Department of Basic Medical Sciences, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok, 10300, Thailand.
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.
Insights
Fluoxetine may impair pancreatic beta-cell function. This study used metabolomics to show fluoxetine perturbs the citric acid cycle in MIN6 cells, offering insights into its cellular effects.
Area of Science:
- Cellular biology
- Metabolomics
- Pharmacology
Background:
- Fluoxetine use is linked to pancreatic beta-cell dysfunction.
- The precise mechanism of fluoxetine's action on beta cells remains unclear.
Purpose of the Study:
- To investigate the cellular response of MIN6 cells to fluoxetine.
- To elucidate the molecular mechanisms underlying fluoxetine's effects on beta cells using metabolomics.
Main Methods:
- Untargeted cell-based metabolomics was employed.
- MIN6 cells were treated with fluoxetine.
- Metabolic profiling was conducted using liquid chromatography-high resolution mass spectrometry (LC-HRMS).
- Data analysis involved principal component analysis and discriminant analyses.
Main Results:
- Sixty-six differentially expressed metabolites were identified between control and fluoxetine-treated groups.
- Fluoxetine treatment significantly perturbed the citric acid cycle in MIN6 cells.
Conclusions:
- This study provides novel insights into the molecular mechanisms of fluoxetine's impact on pancreatic beta cells.
- The findings highlight the perturbation of the citric acid cycle as a key cellular response to fluoxetine.
