ArticleJournal of psychiatry & neuroscience : JPN2017
In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact.
Article in Journal of psychiatry & neuroscience : JPN, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- A hypothalamus-liver-skeletal muscle axis controlled by JNK1 and FGF21 mediates olanzapine-induced insulin resistance in an intraperitoneal treatment in male mice.Redox biology · 2026Article
- Effects of antipsychotics on brain insulin action in females: Study protocol for a placebo-controlled, crossover neuroimaging study.PloS one · 2026Article
- Drawbacks of Olanzapine Therapy: An Emphasis on Its Metabolic Effects and Discontinuation.Journal of clinical medicine · 2025Review
- Protective effects of central leptin on whole-body energy homeostasis upon acute olanzapine exposure.bioRxiv : the preprint server for biology · 2025Article
- Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway.The EMBO journal · 2025Article
- Development of Novel Tools for Dissection of Central Versus Peripheral Dopamine D2-Like Receptor Signaling in Dysglycemia.Diabetes · 2024Article
- Olanzapine's effects on hypothalamic transcriptomics and kinase activity.Psychoneuroendocrinology · 2024Article
- In vivo techniques for assessment of insulin sensitivity and glucose metabolism.The Journal of endocrinology · 2024Review
- Antipsychotics impair regulation of glucose metabolism by central glucose.Molecular psychiatry · 2022Article
- Article
- Newly proposed insulin resistance indexes called TyG-NC and TyG-NHtR show efficacy in diagnosing the metabolic syndrome.Journal of endocrinological investigation · 2021Article
- Macrophage-derived secretome is sufficient to confer olanzapine-mediated insulin resistance in human adipocytes.Comprehensive psychoneuroendocrinology · 2021Article
- A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models.PloS one · 2021Article
- A Focused Review of the Metabolic Side-Effects of Clozapine.Frontiers in endocrinology · 2021Review
- A targeted neurotransmitter quantification and nontargeted metabolic profiling method for pharmacometabolomics analysis of olanzapine by using UPLC-HRMS.RSC advances · 2020Article
- Differential Effects of Acute Treatment With Antipsychotic Drugs on Peripheral Catecholamines.Frontiers in psychiatry · 2020Article
- Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain.Cells · 2019Review
- Samidorphan mitigates olanzapine-induced weight gain and metabolic dysfunction in rats and non-human primates.Journal of psychopharmacology (Oxford, England) · 2019Article
- Chronic olanzapine administration causes metabolic syndrome through inflammatory cytokines in rodent models of insulin resistance.Scientific reports · 2019Article
- Preclinical and Clinical Sex Differences in Antipsychotic-Induced Metabolic Disturbances: A Narrative Review of Adiposity and Glucose Metabolism.Journal of psychiatry and brain science · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInsulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms. Here, we examined whether antipsychotics disrupt central insulin action, hypothesizing that olanzapine would impair the well-established ability of central insulin to supress hepatic glucose production.
methodsPancreatic euglycemic clamps were used to measure glucose kinetics alongside a central infusion of insulin or vehicle into the third ventricle. Male rats were pretreated with olanzapine or vehicle per our established model of acute olanzapine-induced peripheral insulin resistance. Groups included (central-peripheral) vehicle-vehicle (
resultsThere were no differences in peripheral glucose or insulin levels. Unexpectedly, we showed that central insulin increased glucose uptake, and this effect was not perturbed by olanzapine. We replicated suppression of glucose production by insulin (clamp relative to basal: 77.9% ± 13.1%, all LIMITATIONS: This study used only male rats and an acute dose of olanzapine.
conclusionTo our knowledge, this is the first study suggesting olanzapine may impair central insulin sensing, elucidating a potential mechanism of antipsychotic-induced diabetes and opening avenues of investigation related to domains of schizophrenia psychopathology.
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29083297PMC5662464W2766496673What OpenQuestion holds
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.