Departamento de Bioquímica-Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade Cx. Postal 069, CEP: 88040-970 Florianópolis, SC, Brazil.
Eur J Pharmacol. 2013 Feb 28;702(1-3):264-8. doi: 10.1016/j.ejphar.2013.01.055. Epub 2013 Feb 8.
Rutin is a flavonol glycoside with multiple biological activities and it has been demonstrated that rutin modulates glucose homeostasis. In pancreatic β-cell, an increase in intracellular calcium concentration triggers exocytosis and thus insulin secretion. The aim of the study reported herein was to investigate the effect of rutin associated intracellular pathways on Ca(2+) uptake in isolated rat pancreatic islets. We focused on the acute effects of rutin on in vivo insulin secretion and the in vitro cellular signaling of pancreatic islets related to this effect. The results show that rutin significantly increased glucose-induced insulin secretion in an in vivo treatment. Moreover, it was demonstrated that rutin stimulated Ca(2+) uptake after 10 min of incubation compared with the respective control group. The involvement of L-type voltage-dependent Ca(2+) channels (L-VDCCs) was evidenced using nifedipine, while the use of glibenclamide and diazoxide demonstrated that the ATP-sensitive potassium (KATP) channels are not involved in the rutin action in pancreatic islets. In conclusion, rutin diminish glycemia, potentiate insulin secretion in vivo and significantly stimulates Ca(2+) uptake in rat pancreatic islets. A novel cellular mechanism of action of rutin in Ca(2+) uptake on pancreatic β-cells was elucidated. Rutin modulates Ca(2+) uptake in pancreatic islets by opening L-VDCCs, alter intracellular Ca(2+), PLC and PKC signaling pathways, characterizing KATP channel-independent pathways. These findings highlight rutin, a dietary adjuvant, as a potential insulin secretagogue contributing to glucose homeostasis.
芦丁是一种具有多种生物活性的类黄酮糖苷，已证实芦丁能调节葡萄糖稳态。在胰腺β细胞中，细胞内钙离子浓度的增加会引发胞吐作用，从而导致胰岛素分泌。本研究旨在探讨芦丁相关细胞内途径对分离的大鼠胰岛细胞内 Ca(2+)摄取的影响。我们专注于芦丁对体内胰岛素分泌的急性影响，以及与这种作用相关的胰岛细胞的体外细胞信号转导。结果表明，芦丁在体内治疗中显著增加了葡萄糖诱导的胰岛素分泌。此外，与相应的对照组相比，芦丁在孵育 10 分钟后刺激 Ca(2+)摄取。使用硝苯地平证实了 L 型电压依赖性 Ca(2+)通道 (L-VDCCs) 的参与，而使用格列本脲和二氮嗪表明，ATP 敏感性钾 (KATP) 通道不参与芦丁在胰岛中的作用。总之，芦丁降低血糖，增强体内胰岛素分泌，并显著刺激大鼠胰岛细胞内的 Ca(2+)摄取。阐明了芦丁在胰腺β细胞内 Ca(2+)摄取中的新的细胞作用机制。芦丁通过打开 L-VDCCs 调节胰岛细胞内 Ca(2+)摄取，改变细胞内 Ca(2+)、PLC 和 PKC 信号通路，表征 KATP 通道非依赖性途径。这些发现强调了芦丁作为一种潜在的胰岛素分泌剂，作为膳食佐剂有助于葡萄糖稳态。
