ArticleDiabetologia2008
Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- 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
- Sex-Specific Effects of Long-Term Antipsychotic Drug Treatment on Adipocyte Tissue and the Crosstalk to Liver and Brain in Rats.International journal of molecular sciences · 2024Article
- Diabetic Ketoacidosis Associated With Second Generation Antipsychotics: A Case Study and Review of Literature.Psychiatry investigation · 2024Article
- Selective 5-HTPharmaceuticals (Basel, Switzerland) · 2023Article
- Roles of Pancreatic Islet Catecholamine Neurotransmitters in Glycemic Control and in Antipsychotic Drug-Induced Dysglycemia.Diabetes · 2023Review
- Antipsychotic Drug-Induced Increases in Peripheral Catecholamines are Associated With Glucose Intolerance.Frontiers in pharmacology · 2022Article
- Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors.Translational psychiatry · 2021Article
- A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models.PloS one · 2021Article
- 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
- Sex-dependent alterations of dopamine receptor and glucose transporter density in rat hypothalamus under long-term clozapine and haloperidol medication.Brain and behavior · 2020Article
- Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics.Frontiers in endocrinology · 2020Review
- Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain.Cells · 2019Review
- Atypical antipsychotics-induced metabolic syndrome and nonalcoholic fatty liver disease: a critical review.Neuropsychiatric disease and treatment · 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
- Disrupted sphingolipid metabolism following acute clozapine and olanzapine administration.Journal of biomedical science · 2018Article
- Olanzapine-induced Cataract in a Teenage Girl.Cureus · 2018Article
- In male rats, the ability of central insulin to suppress glucose production is impaired by olanzapine, whereas glucose uptake is left intact.Journal of psychiatry & neuroscience : JPN · 2017Article
- Haloperidol affects bones while clozapine alters metabolic parameters - sex specific effects in rats perinatally treated with phencyclidine.BMC pharmacology & toxicology · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisUse of the second-generation antipsychotic drugs (SGAs) results in the development of obesity and a type 2 diabetes-like syndrome. We hypothesised that, in addition to the insulin resistance associated with the obesity, the SGAs might have acute effects on glucose metabolism that could contribute to the derangements in glucose metabolism.
methodsWe investigated the effects of therapeutically relevant levels of three different antipsychotic medications (haloperidol, quetiapine and clozapine) on glucose tolerance, measures of insulin resistance and hepatic glucose production, and on insulin and glucagon secretion in rats.
resultsWe found that these drugs induce impaired glucose tolerance in rats that is associated with increased insulin secretion (clozapine>quetiapine>haloperidol) but is independent of weight gain. However, Akt/protein kinase B activation is normal, and at these levels of drug there was no effect on insulin action in fat cells or soleus muscle, and no effect on insulin sensitivity as evaluated by insulin tolerance tests. We show that clozapine induces increased glucose levels following pyruvate and glycerol challenges, indicating an increase in hepatic glucose output (HGO). Increased HGO would in turn increase insulin release and would explain the apparent phenotype mimicking insulin resistance. We provide evidence that this effect could at least in part be mediated by a stimulation of glucagon secretion. CONCLUSIONS/
interpretationOur findings indicate that SGAs can cause acute derangements in glucose metabolism that are not caused by a direct induction of insulin resistance but act via an increase in glucagon secretion and thus stimulation of hepatic glucose production.
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