ArticleActa pharmacologica Sinica2014
Co-administration of paroxetine and pravastatin causes deregulation of glucose homeostasis in diabetic rats via enhanced paroxetine exposure.
Article in Acta pharmacologica Sinica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Clozapine impaired glucose-stimulated insulin secretion partly by increasing plasma 5-HT levels due to the inhibition of OCT1-mediated hepatic 5-HT uptake in mice.Acta pharmacologica Sinica · 2025Article
- Luteolin suppresses 5-hydroxytryptamine elevation in stimulated RBL-2H3 cells and experimental colitis mice.Journal of clinical biochemistry and nutrition · 2021Article
- Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus.BioMed research international · 2021Review
- Interpretation of Drug Interaction Using Systemic and Local Tissue Exposure Changes.Pharmaceutics · 2020Review
- Characteristics of β-oxidative and reductive metabolism on the acyl side chain of cinnamic acid and its analogues in rats.Acta pharmacologica Sinica · 2019Article
- The Next Generation of Drug Safety Science: Coupling Detection, Corroboration, and Validation to Discover Novel Drug Effects and Drug-Drug Interactions.Clinical pharmacology and therapeutics · 2018Article
- Impact of Muscarinic MCNS drugs · 2017Article
- The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1.Scientific reports · 2016Article
- Sesamol: a Treatment for Diabetes-Associated Blood-Brain Barrier Dysfunction.Postdoc journal : a journal of postdoctoral research and postdoctoral affairs · 2014Article
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10 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
aimClinical evidence shows that co-administration of pravastatin and paroxetine deregulates glucose homeostasis in diabetic patients. The aim of this study was to verify this phenomenon in diabetic rats and to elucidate the underlying mechanisms.
methodsDiabetes mellitus was induced in male SD rats by a high-fat diet combined with a low-dose streptozotocin injection. The rats were orally administered paroxetine (10 mg/kg) and pravastatin (10 mg/d) or both the drugs daily for 28 d. The pharmacokinetics of paroxetine and pravastatin were examined on d 1 and d 28. Biochemical parameters including serum insulin, glucose and lipids were monitored during the treatments. An insulin-secreting cell line (INS-1) was used for measuring insulin secretion.
resultsIn diabetic rats, co-administration of paroxetine and pravastatin markedly increased the concentrations of both the drugs compared with administration of each drug alone. Furthermore, co-administration severely impaired glucose homeostasis in diabetic rats, as demonstrated by significantly increased serum glucose level, decreased serum and pancreatic insulin levels, and decreased pancreatic Insulin-2 mRNA and tryptophan hydroxylase-1 (Tph-1) mRNA levels. Treatment of INS-1 cells with paroxetine (5 and 10 μmol/L) significantly inhibited insulin secretion, decreased the intracellular insulin, 5-HT, Insulin-2 mRNA and Tph-1 mRNA levels. Treatment of the cells with pravastatin (10 μmol/L) significantly stimulated insulin secretion, which was weakened by co-treatment with paroxetine.
conclusionParoxetine inhibits insulin secretion at least via decreasing intracellular 5-HT and insulin biosynthesis. The deregulation of glucose homeostasis by co-administration of paroxetine and pravastatin in diabetic rats can be attributed to enhanced paroxetine exposure.
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