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标题：Blockade of multiple monoamines receptors reduce insulin secretion from pancreatic β-cells
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作者：Mao Nagata ; Tomoharu Yokooji ; Tomoe Nakai 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-10
DOI：10.1038/s41598-019-52590-y
出版社：Springer Nature
摘要：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 2 , D 3 and D 4 ), serotonin (5-HT 2A , 5-HT 2B , 5-HT 2C , and 5-HT 6 ), and histamine (H 1 and H 2 ) receptors in HIT-T15 cells. Olanzapine decreased insulin secretion from HIT-T15 cells at clinically relevant concentrations (64-160 nM). A dopamine D 2 agonist, D 3 antagonist, and D 4 antagonist suppressed insulin secretion, whereas a D 2 antagonist and D 3 agonist increased it. A serotonin 5-HT 2B agonist slightly increased insulin secretion, while a 5-HT 2C antagonist slightly decreased it. Other agonists and antagonists for serotonin receptors did not affect insulin secretion. A histamine H 1 agonist increased insulin secretion, whereas an H 1 antagonist and H 2 agonist suppressed it. Our results suggest that dopamine (D 2 , D 3 and D 4 ), serotonin (5-HT 2B and 5-HT 2C ), and histamine (H 1 and H 2 ) 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 3 , serotonin 5-HT 2B and 5-HT 2C , and histamine H 1 receptors.