Comparative efficacy, toxicity, and insulin-suppressive effects of simvastatin and pravastatin in fatty acid-challenged mouse insulinoma MIN6 β-cell model

Our 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.

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Publication Details

Journal
Frontiers in Endocrinology
Published
2024-10-31
DOI
https://doi.org/10.3389/fendo.2024.1383448
Primary Topic
Lipoproteins and Cardiovascular Health
Type
article
Field-Weighted Citation Impact
0.00

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article

Comparative efficacy, toxicity, and insulin-suppressive effects of simvastatin and pravastatin in fatty acid-challenged mouse insulinoma MIN6 β-cell model

Ashraf Al Madhoun, Fatemah Bahman, Rasheed Ahmad, Fahd Al‐Mulla et al.
Frontiers in Endocrinology
Lipoproteins and Cardiovascular Health
article

Comparative efficacy, toxicity, and insulin-suppressive effects of simvastatin and pravastatin in fatty acid-challenged mouse insulinoma MIN6 β-cell model

Ashraf Al Madhoun, Fatemah Bahman, Rasheed Ahmad, Fahd Al‐Mulla, Fawaz Alzaïd, Sardar Sindhu, Michayla R. Williams, Hossein Arefanian, Nourah Almansour, Shaima Albeloushi, Fatema Al‐Rashed, Mohammed Qaddoumi
article en

Abstract

Our 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.

Frontiers in EndocrinologyVol. 15
Inserm (FR), Université Paris Cité (FR), Kuwait University (KW), Institut Necker Enfants Malades (FR), Dasman Diabetes Institute (KW)
Kuwait Foundation for the Advancement of Sciences, Dasman Diabetes Institute
Good health and well-being
Openalex Percentile: Top 63%
Lipoproteins and Cardiovascular Health
DOIOpen Access PDFOpenAlex
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