Olanzapine-Induced Hyperglycemia: Possible Involvement of Histaminergic, Dopaminergic and Adrenergic Functions in the Central Nervous System
| العنوان: | Olanzapine-Induced Hyperglycemia: Possible Involvement of Histaminergic, Dopaminergic and Adrenergic Functions in the Central Nervous System |
|---|---|
| المؤلفون: | Mamiko Osada, Misa Kai, Atsuko Kamei, Takahiro Ohashi, Megumi Ikegami, Junzo Kamei, Hiroko Ikeda |
| المصدر: | Neuroendocrinology. 98:224-232 |
| بيانات النشر: | S. Karger AG, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Blood Glucose, Central Nervous System, Male, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, Hypothalamus, Atypical antipsychotic, Histamine H1 receptor, Pharmacology, Benzodiazepines, Mice, Cellular and Molecular Neuroscience, Endocrinology, Receptors, Adrenergic, alpha-1, Dopamine receptor D2, Internal medicine, medicine, Prazosin, Animals, Receptors, Histamine H1, Mice, Inbred ICR, Receptors, Dopamine D2, Endocrine and Autonomic Systems, Chemistry, Histaminergic, AMPK, Muscarinic acetylcholine receptor M1, Receptor antagonist, Dopamine D2 Receptor Antagonists, Olanzapine, Hyperglycemia, Antipsychotic Agents, medicine.drug |
| الوصف: | Background/Aims: Atypical antipsychotic drugs such as olanzapine are known to induce metabolic disturbance. We have already shown that olanzapine induces hepatic glucose production through the activation of hypothalamic adenosine 5′-monophosphate-activated protein kinase (AMPK). However, it is unclear how olanzapine activates hypothalamic AMPK. Since olanzapine is known to antagonize several receptors, including histaminergic, muscarinic, serotonergic, dopaminergic and adrenergic receptors, we examined the effect of each receptor antagonist on blood glucose levels in mice. Moreover, we also investigated whether these antagonists activate hypothalamic AMPK. Methods: Male 6-week-old ICR mice were used. Blood glucose levels were determined by the glucose oxidase method. AMPK expression was measured by Western blotting. Results: Central administration of olanzapine (5-15 nmol i.c.v.) dose-dependently increased blood glucose levels in mice, whereas olanzapine did not change blood insulin levels. Histamine H1 receptor antagonist chlorpheniramine (1-10 μg i.c.v.), dopamine D2 receptor antagonist L-sulpiride (1-10 μg i.c.v.) and α1-adrenoceptor antagonist prazosin (0.3-3 μg i.c.v.) also significantly increased blood glucose levels in mice. In contrast, the blood glucose levels were not affected by muscarinic M1 receptor antagonist dicyclomine (1-10 μg i.c.v.) or serotonin 5-HT2A receptor antagonist M100907 (1-10 ng i.c.v.). Olanzapine-induced hyperglycemia was inhibited by the AMPK inhibitor compound C, and AMPK activator AICAR (10 ng to 1 μg i.c.v.) significantly increased blood glucose levels. Olanzapine (15 nmol), chlorpheniramine (10 μg), L-sulpiride (10 μg) and prazosin (3 μg) significantly increased phosphorylated AMPK in the hypothalamus of mice. Conclusion: These results suggest that olanzapine activates hypothalamic AMPK by antagonizing histamine H1 receptors, dopamine D2 receptors and α1-adrenoceptors, which induces hyperglycemia. |
| تدمد: | 1423-0194 0028-3835 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::380466b6ec73586ebd79a973c35e4a6bTest https://doi.org/10.1159/000356119Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....380466b6ec73586ebd79a973c35e4a6b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14230194 00283835 |
|---|