ArticlePsychopharmacology2014
The activation of the Akt/PKB signalling pathway in the brains of clozapine-exposed rats is linked to hyperinsulinemia and not a direct drug effect.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Recurrent reactive hypoglycemia due to clozapine-induced glucose intolerance: A case report.PCN reports : psychiatry and clinical neurosciences · 2023Article
- Clozapine Induced Disturbances in Hepatic Glucose Metabolism: The Potential Role of PGRMC1 Signaling.Frontiers in endocrinology · 2021Article
- A Working Hypothesis Regarding Identical Pathomechanisms between Clinical Efficacy and Adverse Reaction of Clozapine via the Activation of Connexin43.International journal of molecular sciences · 2020Review
- Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain.Cells · 2019Review
- Clozapine-dependent inhibition of EGF/neuregulin receptor (ErbB) kinases.Translational psychiatry · 2019Article
- Association of Protein Kinase B (AKT) DNA Hypermethylation with Maintenance Atypical Antipsychotic Treatment in Patients with Bipolar Disorder.Pharmacotherapy · 2018Observational
- Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.International journal of molecular sciences · 2016Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The second generation antipsychotic drug clozapine is a much more effective therapy for schizophrenia than first generation compounds, but the reasons for this are poorly understood. We have previously shown that one distinguishing feature of clozapine is its ability to raise glucagon levels in animal models and thus causes prolonged hyperinsulinemia without inducing hypoglycaemia. Previous studies have provided evidence that defects in Akt/PKB and GSK3 signalling can contribute to development of psychiatric diseases. Clozapine is known to activate Akt/PKB in the brain, and some studies have indicated that this is due to a direct effect of the drug on the neurons. However, we provide strong evidence that elevated insulin levels induced by clozapine are in fact the real cause of the drug's effects on Akt/PKB and GSK3 in the brain. This suggests that the elevated levels of insulin induced by clozapine may contribute to this drug's therapeutic efficacy.
Indexed as
Identifiers
What 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.