Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Ngamratanapaiboon S

PROVIDER: S-EPMC10568956 | biostudies-literature | 2023 Sep-Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ngamratanapaiboon Surachai S Pornchokchai Krittaboon K Wongpitoonmanachai Siriphattarinya S Pholkla Petchlada P Srikornvit Napatarin N Mo Jiajun J Hongthawonsiri Patipol P Yambangyang Pracha P Akrachalanont Pilaslak P

Research in pharmaceutical sciences 20230820 5

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Metabolic profiling of MIN6 cells was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis on samples prepared under optim ...[more]

PMID: 37842516

Similar Datasets

Project description:Hyperglycemia causes mitochondrial damage renal tubular cells, which contribute to the progression of diabetic kidney disease. However, the metabolic aberration of renal tubular cells in an hyperglycemic milieu has not been fully elucidated. In this study, human proximal renal tubular cell line (HK-2 cell) are incubated in glucose and mannitol at 5 mM or 25 mM. Cellular metabolome was determined by capillary electrophoresis time of flight mass spectrometer (CE-TOF/MS) and capillary electrophoresis-triple quadrupole mass spectrometry (CE-QqQMS). A total of 116 metabolites were quantified. Principal component analysis (PCA) revealed excellent clustering of metabolomic changes for different treatment conditions, and exposure to glucose at 5 and 25 mM lead to distinct metabolomic profiles as compared to samples treated with serum-free medium or mannitol as osmotic control. Hierarchical clustering analysis showed a number of characteristic changes in metabolic profile following exposure to 5 mM or 25 mM glucose. Notably, lactate-to-pyruvate ratio was significantly increased, while cellular levels of citric acid, α-ketoglutaric acid (i.e. 2-oxoglutaric acid), and fumaric acid were significantly reduced after exposure to glucose at 25 mM but not 5 mM. Moreover, cellular levels of reduced glutathione and total glutathione were significantly decreased, and S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio was significantly increased after exposure to glucose 25 mM but not 5 mM. We conclude that in response to high glucose, HK-2 cells characteristic metabolomic changes, including increase in lactate-to-pyruvate ratio, reduction in Krebs cycle metabolites, reduction in glutathione antioxidant activity, and increase in cellular methylation potential. Our results may shed light on the pathogenesis of diabetic kidney disease, but the expression of glucose metabolism-related protein and enzyme activity in HK-2 cells after hyperglycemia condition need to be confirmed by further studies.

Project description:IntroductionFamilial hypercholesterolemia, the highly prevalent form of dyslipidemia, is a well-known risk factor for premature heart disease and stroke worldwide. Statins, which inhibit 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, are the first-choice treatment for dyslipidemias, and have been effective in reducing the risk of stroke and myocardial infarction. However, emerging evidence indicates that statins may increase the incidence of new-onset type 2 diabetes by reducing β-cell mass and function. Notably, past in vitro reports studying the effects of statins on β-cells were performed without including free fatty acids in the model. This factor should have been addressed since these agents are used to treat individuals with hyperlipidemia.MethodsHere, we used a mouse insulinoma MIN6 β-cell culture model to assess the efficacy, cytotoxicity, and insulin-suppressive effects of simvastatin and pravastatin in the presence of palmitic, linoleic, and oleic acids cocktail to mimic mixed lipids challenge in a biologically relevant setting.Results and discussionOur findings indicate that simvastatin was more effective in lowering intracellular cholesterol but was more cytotoxic as compared to pravastatin. Similarly, simvastatin exhibited a higher suppression of total insulin content and insulin secretion. Both drugs suppressed insulin secretion in phases 1 and 2, dose-dependently. No significant effect was observed on mitochondrial respiration. More importantly, elution experiments showed that insulin content diminution by simvastatin treatment was reversible, while exogenous mevalonate did not improve total insulin content. This suggests that simvastatin's influence on insulin content is independent of its specific inhibitory action on HMG-CoA reductase. In conclusion, our study identified that simvastatin was more effective in lowering intracellular cholesterol, albeit it was more toxic and suppressive of β-cells function. Notably, this suppression was found to be reversible.

Dataset Information

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

Background and purpose

Experimental approach

Findings/results

Conclusion and implications

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets