ArticleeLife2020
Antipsychotic olanzapine-induced misfolding of proinsulin in the endoplasmic reticulum accounts for atypical development of diabetes.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Non-pharmacological interventions for antipsychotic drug-related metabolic abnormalities: a systematic narrative review.BMC psychiatry · 2026Pooled it
- Olanzapine and the Spectrum of Drug-induced Diabetes: Unveiling Dual Risk Factors for Type 2 Diabetes and Acute-onset Ketoacidosis.Internal medicine (Tokyo, Japan) · 2026Review
- Urinary Retention Triggered by Urethritis in Olanzapine-induced Diabetic Ketoacidosis.Internal medicine (Tokyo, Japan) · 2026Review
- Risk of diabetes mellitus with olanzapine compared to clozapine: A systematic review and meta-analysis.PCN reports : psychiatry and clinical neurosciences · 2025Article
- CaNature cell biology · 2025Article
- Metal-Responsive Up-Regulation of Bifunctional Disulfides for Suppressing Protein Misfolding and Promoting Oxidative Folding.Angewandte Chemie (International ed. in English) · 2025Article
- Quantification of Folded and Misfolded Proinsulin Forms Using Nonreducing SDS-PAGE and Proinsulin-Specific Immunoblotting.Bio-protocol · 2025Article
- Drug-induced severe sideroblastic anemia following combined olanzapine and fluvoxamine therapy: a case report.Frontiers in psychiatry · 2025Article
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- UGGT1-mediated reglucosylation ofeLife · 2024Article
- Olanzapine's effects on hypothalamic transcriptomics and kinase activity.Psychoneuroendocrinology · 2024Article
- Proinsulin folding and trafficking defects trigger a common pathological disturbance of endoplasmic reticulum homeostasis.Protein science : a publication of the Protein Society · 2024Article
- Enzymatic and synthetic regulation of polypeptide folding.Chemical science · 2024Review
- microRNAs slow translating ribosomes to prevent protein misfolding in eukaryotes.The EMBO journal · 2023Article
- Case report: Olanzapine-associated water retention, high blood pressure, and subsequent preterm preeclampsia.Frontiers in psychiatry · 2023Article
- Cysteine-based protein folding modulators for trapping intermediates and misfolded forms.RSC advances · 2022Article
- [Bioinformatic analysis of differentially expressed proteins in the dorsal raphe nucleus of rats after continuous treatment with olanzapine].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Attenuation of Olanzapine-Induced Endoplasmic Reticulum Stress Improves Insulin Secretion in Pancreatic Beta Cells.Metabolites · 2022Article
- Olanzapine-associated dose-dependent alterations for weight and metabolic parameters in a prospective cohort.Basic & clinical pharmacology & toxicology · 2022Article
- Oligomannose-Type Glycan Processing in the Endoplasmic Reticulum and Its Importance in Misfolding Diseases.Biology · 2022Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Second-generation antipsychotics are widely used to medicate patients with schizophrenia, but may cause metabolic side effects such as diabetes, which has been considered to result from obesity-associated insulin resistance. Olanzapine is particularly well known for this effect. However, clinical studies have suggested that olanzapine-induced hyperglycemia in certain patients cannot be explained by such a generalized mechanism. Here, we focused on the effects of olanzapine on insulin biosynthesis and secretion by mouse insulinoma MIN6 cells. Olanzapine reduced maturation of proinsulin, and thereby inhibited secretion of insulin; and specifically shifted the primary localization of proinsulin from insulin granules to the endoplasmic reticulum. This was due to olanzapine's impairment of proper disulfide bond formation in proinsulin, although direct targets of olanzapine remain undetermined. Olanzapine-induced proinsulin misfolding and subsequent decrease also occurred at the mouse level. This mechanism of olanzapine-induced β-cell dysfunction should be considered, together with weight gain, when patients are administered olanzapine.
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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.