Abstract：
There is increasing evidence linking bitter taste receptor (BTR) signaling to gut hormone secretion and glucose homeostasis. However, its effect on islet hormone secretion has been poorly characterized. This study investigated the effect of the bitter substance, denatonium benzoate (DB), on hormone secretion from mouse pancreatic islets and INS-1 832/13 cells. DB (0.5-1 mM) augmented insulin secretion at both 2.8 mM and 16.7 mM glucose. This effect was no longer present at 5 mM DB likely due to the greater levels of cellular apoptosis. DB-stimulated insulin secretion involved closure of the KATP channel, activation of T2R signaling in beta-cells, and intraislet glucagon-like peptide-1 (GLP-1) release. DB also enhanced glucagon and somatostatin secretion, but the underlying mechanism was less clear. Together, this study demonstrates that the bitter substance, DB, is a strong potentiator of islet hormone secretion independent of glucose. This observation highlights the potential for widespread off-target effects associated with the clinical use of bitter-tasting substances.NEW & NOTEWORTHY We show that the bitter substance, denatonium benzoate (DB), stimulates insulin, glucagon, somatostatin, and GLP-1 secretion from pancreatic islets, independent of glucose, and that DB augments insulin release via the KATP channel, bitter taste receptor signaling, and intraislet GLP-1 secretion. Exposure to a high dose of DB (5 mM) induces cellular apoptosis in pancreatic islets. Therefore, clinical use of bitter substances to improve glucose homeostasis may have unintended negative impacts beyond the gut.
摘要：
越来越多的证据表明苦味受体（BTR）信号与肠道激素分泌和葡萄糖稳态有关。然而,它对胰岛激素分泌的影响一直没有得到很好的表征。这项研究调查了苦味物质的作用，苯苯甲酸酯（DB），对小鼠胰岛和INS-1832/13细胞分泌激素的影响。在2.8mM和16.7mM葡萄糖下,DB(0.5-1mM)增强胰岛素分泌。这种效应在5mMDB下不再存在,可能是由于更高水平的细胞凋亡。DB刺激的胰岛素分泌涉及KATP通道的关闭，β细胞中T2R信号的激活，和胰岛内胰高血糖素样肽-1（GLP-1）释放。DB还增强了胰高血糖素和生长抑素的分泌，但潜在的机制尚不清楚。一起,这项研究表明，苦味物质，DB,是独立于葡萄糖的胰岛激素分泌的强增效剂。这一观察结果突出了与苦味物质的临床使用相关的广泛脱靶效应的可能性。我们证明了苦涩的物质，苯苯甲酸酯（DB），胰岛素刺激，胰高血糖素,生长抑素,和胰岛分泌的GLP-1，独立于葡萄糖，DB通过KATP通道增加胰岛素释放，苦味受体信号，和胰岛内GLP-1分泌。暴露于高剂量的DB(5mM)诱导胰岛细胞凋亡。因此,临床使用苦味物质改善葡萄糖稳态可能会对肠道产生意想不到的负面影响.
