ArticlePloS one2015
Simvastatin Impairs Insulin Secretion by Multiple Mechanisms in MIN6 Cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Advances in statin adverse reactions and the potential mechanisms: A systematic review.Journal of advanced research · 2025Pooled it
- Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis.Cardiorenal medicine · 2018 · on this mapPooled it
- Metabolic, enterohepatic and gut microbial effects of atorvastatin in healthy men.Endocrine connections · 2026Article
- From cholesterol to glucose: uncovering how statins induce β-cell dysfunction to promote type 2 diabetes.The Journal of endocrinology · 2025Review
- Ryanodine Receptors in Islet Cell Function: Calcium Signaling, Hormone Secretion, and Diabetes.Cells · 2025Review
- Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells.eLife · 2025Article
- Comparative efficacy, toxicity, and insulin-suppressive effects of simvastatin and pravastatin in fatty acid-challenged mouse insulinoma MIN6 β-cell model.Frontiers in endocrinology · 2024Article
- Article
- Statins and risk of type 2 diabetes: mechanism and clinical implications.Frontiers in endocrinology · 2023Review
- Exenatide prevents statin-related LDL receptor increase and improves insulin secretion in pancreatic beta cells (1.1E7) in a protein kinase A-dependent manner.Journal of applied biomedicine · 2022Article
- Updated Understanding of the Crosstalk Between Glucose/Insulin and Cholesterol Metabolism.Frontiers in cardiovascular medicine · 2022Review
- Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia.International journal of molecular sciences · 2021Article
- Association between Statin Therapy and Lower Incidence of Hyperglycemia in Patients Hospitalized with Acute Coronary Syndromes.Arquivos brasileiros de cardiologia · 2021Article
- The systemic implication of novel non-statin therapies in cardiovascular diabetology: PCSK9 as a case model.Cardiovascular endocrinology & metabolism · 2020Review
- Effects of Polyphenols on Insulin Resistance.Nutrients · 2020Review
- Possible New Strategies for the Treatment of Congenital Hyperinsulinism.Frontiers in endocrinology · 2020Article
- Association of statin therapy with incidence of type 2 diabetes among US Veterans.Journal of clinical cardiology and cardiovascular therapy · 2019Article
- Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells.Journal of diabetes research · 2019Article
- Functional Implications of HMG-CoA Reductase Inhibition on Glucose Metabolism.Korean circulation journal · 2018Review
- Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy.Cardiovascular diabetology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statins are widely used in the treatment of hypercholesterolemia and are efficient in the prevention of cardiovascular disease. Molecular mechanisms explaining statin-induced impairment in insulin secretion remain largely unknown. In the current study, we show that simvastatin decreased glucose-stimulated insulin secretion in mouse pancreatic MIN6 β-cells by 59% and 79% (p<0.01) at glucose concentration of 5.5 mmol/l and 16.7 mmol/l, respectively, compared to control, whereas pravastatin did not impair insulin secretion. Simvastatin induced decrease in insulin secretion occurred through multiple targets. In addition to its established effects on ATP-sensitive potassium channels (p = 0.004) and voltage-gated calcium channels (p = 0.004), simvastatin suppressed insulin secretion stimulated by muscarinic M3 or GPR40 receptor agonists (Tak875 by 33%, p = 0.002; GW9508 by 77%, p = 0.01) at glucose level of 5.5 mmol/l, and inhibited calcium release from the endoplasmic reticulum. Impaired insulin secretion caused by simvastatin treatment were efficiently restored by GPR119 or GLP-1 receptor stimulation and by direct activation of cAMP-dependent signaling pathways with forskolin. The effects of simvastatin treatment on insulin secretion were not affected by the presence of hyperglycemia. Our observation of the opposite effects of simvastatin and pravastatin on glucose-stimulated insulin secretion is in agreement with previous reports showing that simvastatin, but not pravastatin, was associated with increased risk of incident diabetes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.