Scientific reports, 2019-11, Vol.9 (1), p.16438-10, Article 16438
2019
Details
- Autor(en) / Beteiligte
- Titel
- Blockade of multiple monoamines receptors reduce insulin secretion from pancreatic β-cells
- Ist Teil von
- Scientific reports, 2019-11, Vol.9 (1), p.16438-10, Article 16438
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Clinical use of olanzapine frequently causes severe hyperglycemia as an adverse effect. In this study, we elucidated mechanisms by which olanzapine reduced insulin secretion using the hamster pancreatic β-cell line HIT-T15. Reverse transcriptional-PCR analysis revealed expression of dopamine (D , D and D ), serotonin (5-HT , 5-HT , 5-HT , and 5-HT ), and histamine (H and H ) receptors in HIT-T15 cells. Olanzapine decreased insulin secretion from HIT-T15 cells at clinically relevant concentrations (64-160 nM). A dopamine D agonist, D antagonist, and D antagonist suppressed insulin secretion, whereas a D antagonist and D agonist increased it. A serotonin 5-HT agonist slightly increased insulin secretion, while a 5-HT antagonist slightly decreased it. Other agonists and antagonists for serotonin receptors did not affect insulin secretion. A histamine H agonist increased insulin secretion, whereas an H antagonist and H agonist suppressed it. Our results suggest that dopamine (D , D and D ), serotonin (5-HT and 5-HT ), and histamine (H and H ) receptors, which are expressed on pancreatic β-cells, directly modulate insulin secretion from pancreatic β-cells. Thus, olanzapine may induce hyperglycemia in clinical settings by suppressing insulin secretion from pancreatic β-cells through inhibition of dopamine D , serotonin 5-HT and 5-HT , and histamine H receptors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-019-52590-yTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6848069
- Format
- –
- Schlagworte
- Agonists, Beta cells, Dopamine, Dopamine D2 receptors, Dopamine D3 receptors, Dopamine D4 receptors, Glucose, Histamine H1 receptors, Hyperglycemia, Insulin, Insulin secretion, Insulin Secretion - drug effects, Insulin-Secreting Cells - drug effects, Insulin-Secreting Cells - metabolism, Monoamines, Olanzapine, Pancreas, Potassium, Receptors, Biogenic Amine - antagonists & inhibitors, Receptors, Biogenic Amine - genetics, Receptors, Biogenic Amine - metabolism, Receptors, Dopamine - genetics, Receptors, Dopamine - metabolism, Receptors, Histamine - genetics, Receptors, Histamine - metabolism, Receptors, Serotonin - genetics, Receptors, Serotonin - metabolism, RNA, Messenger - genetics, Secretion, Serotonin, Serotonin receptors, Serotonin S2 receptors, Serotonin S6 receptors