ArticleThe Journal of biological chemistry2013
Selective serotonin reuptake inhibitors (SSRIs) inhibit insulin secretion and action in pancreatic β cells.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
39 citing papers in PubMed, 87 citations in OpenAlex.
- The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Impact of selective serotonin reuptake inhibitors on major salivary glands and mandibular alveolar bone; a histological, histochemical and biochemical study.BMC oral health · 2026Article
- The impact of sertraline treatment on obesity, inflammation, blood pressure, and lipid profiles: a systematic review and meta-analysis of randomized controlled trials.Diabetology & metabolic syndrome · 2025Review
- Psychiatric factors predict type 2 diabetes mellitus in US Veterans.Schizophrenia (Heidelberg, Germany) · 2025Article
- Comorbidity of Depression and Diabetes: A Literature Review on Systemic Flaws in Healthcare and the Benefits of Collaborative Diagnosis and Treatment in Primary Care Settings.Current diabetes reviews · 2025Review
- The selective serotonin reuptake inhibitors, sertraline and paroxetine, improve islet beta-cell mass and function in vitro.Diabetes, obesity & metabolism · 2024Article
- Effects of selective serotonin reuptake inhibitors on endocrine system (Review).Biomedical reports · 2024Review
- Management of Pregnant Women with Mental Disorders Requires Attention to Gestational Diabetes Mellitus.Women's health reports (New Rochelle, N.Y.) · 2024Article
- Review
- Antidepressants and type 2 diabetes: highways to knowns and unknowns.Diabetology & metabolic syndrome · 2023Review
- Silymarin attenuates escitalopram (cipralex) induced pancreatic injury in adult male albino rats: a biochemical, histological, and immunohistochemical approach.Anatomy & cell biology · 2023Article
- Glucose and Lipid Profiles Predict Anthropometric Changes in Drug-Naïve Adolescents Starting Treatment with Risperidone or Sertraline: A Pilot Study.Biomedicines · 2022Article
- A seven-transmembrane protein-TM7SF3, resides in nuclear speckles and regulates alternative splicing.iScience · 2022Article
- The selective serotonin reuptake inhibitor fluoxetine has direct effects on beta cells, promoting insulin secretion and increasing beta-cell mass.Diabetes, obesity & metabolism · 2022Article
- Role of Serotonin (5-HT) in GDM Prediction Considering Islet and Liver Interplay in Prediabetic Mice during Gestation.International journal of molecular sciences · 2022Article
- Design, Synthesis, and Characterization of a Novel Fluoroprobe for Live Human Islet Cell Imaging of Serotonin 5-HTChemMedChem · 2022Article
- Association between Depression, Antidepression Medications, and the Risk of Developing Type 2 Diabetes Mellitus: A Nationwide Population-Based Retrospective Cohort Study in Taiwan.BioMed research international · 2021Article
- Fluoxetine regulates glucose and lipid metabolism via the PI3K‑AKT signaling pathway in diabetic rats.Molecular medicine reports · 2020Article
- Food Anticipatory Activity on Circadian Time Scales Is Not Dependent on Central Serotonin: Evidence From Tryptophan Hydroxylase-2 and Serotonin Transporter Knockout Mice.Frontiers in molecular neuroscience · 2020Article
- The Relevance of Glutathione Reductase Inhibition by Fluoxetine to Human Health and Disease: Insights Derived from a Combined Kinetic and Docking Study.The protein journal · 2019Article
Corrections and comments
- Correction · 2018-03-23Error in Image · · see also https://pubpeer.com/publications/BA07C61B3DA3FC433A0F19B03D6B50
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are antidepressants used for the treatment of mood and anxiety disorders. Here, we demonstrate that incubation (2 h) of murine islets or Min6 β cell line with the SSRIs paroxetine, fluoxetine, or sertraline inhibited insulin-induced Tyr phosphorylation of insulin receptor substrate (IRS)-2 protein and the activation of its downstream targets Akt and the ribosomal protein S6 kinase-1 (S6K1). Inhibition was dose-dependent with half-maximal effects at ∼15-20 μM. It correlated with a rapid dephosphorylation and activation of the IRS kinase GSK3β. Introduction of GSK3β siRNAs eliminated the inhibitory effects of the SSRIs. Inhibition of IRS-2 action by 30 μM SSRI was associated with a marked inhibition of glucose-stimulated insulin secretion from murine and human pancreatic islets. Secretion induced by basic secretagogues (KCl and Arg) was not affected by these drugs. Prolonged treatment (16 h) of Min6 cells with sertraline resulted in the induction of inducible nitric oxide synthase; activation of endoplasmic reticulum stress, and the initiation of the unfolded protein response, manifested by enhanced transcription of ATF4 and C/EBP homologous protein. This triggered an apoptotic process, manifested by enhanced caspase 3/7 activity, which resulted in β cell death. These findings implicate SSRIs as inhibitors of IRS protein function and insulin action through the activation of GSK3β. They further suggest that SSRIs inhibit insulin secretion; induce the unfolded protein response; activate an apoptotic process, and trigger β cell death. Given that SSRIs promote insulin resistance while inhibiting insulin secretion, these drugs might accelerate the transition from an insulin-resistant state to overt diabetes.
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Registered trials
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.