Loureirin B promotes insulin secretion through inhibition of KATP channel and influx of intracellular calcium
Loureirin B promotes insulin secretion through inhibition of KATP channel and influx of intracellular calcium
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DOI：
10.1002/jcb.26362
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发表时间：
2018-02-01
影响因子：
4
通讯作者：
Chen, Qin
中科院分区：
文献类型：
--
作者：
Sha, Yijie;Zhang, Yuelin;Chen, Qin
新的糖尿病药物的开发不断探索。从龙血树中提取的一种黄酮类化合物，已被证实能增加胰岛素分泌，降低血糖水平。为了寻找洛瑞素B对胰岛素分泌的促进作用，我们采用了基于细胞实验和计算方法的实验。首先，胰岛素分泌的促进依赖于细胞外葡萄糖浓度。在遗传水平上，褐藻素B提高了Pdx-1和MafA的相对mRNA水平。同时，由于葡萄糖的持续吸收，细胞内ATP水平升高。进一步的实验表明，Ins-1细胞上的K-ATP通道电流被抑制，电压依赖性钙通道随后被激活。Cx43蛋白表达的增加可能介导Ca2+向胞内转移。通过计算模拟，我们假设loureirin B可能与K-ATP通道相互作用，促进胰岛素分泌。综上所述，loureirin B促进胰岛素分泌的主要途径是提高Pdx-1 mRNA水平、MafA水平、细胞内ATP水平、抑制K-ATP电流、抑制Ca2+向细胞内内流。
The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For searching the promotion of insulin secretion with the treatment of loureirin B, experiments were employed based on cell experiments and computational methods. First, promotion of insulin secretion was dependent on extracellular glucose concentration. At the genetic level, loureirin B enhanced the relative mRNA level of Pdx-1 and MafA. Meanwhile the intracellular level of ATP increased due to the continuous absorption of glucose. Further experiments showed that the currents of K-ATP channel on Ins-1 cells were inhibited and the voltage-dependent calcium channels were subsequently activated. The increase of Cx43 protein expression might mediate the Ca2+ to the intracellular. Through computational simulation, we hypothesized that loureirin B might interact with K-ATP channels to promote insulin secretion. In conclusion, it could be concluded that loureirin B promoted insulin secretion mainly through increasing mRNA level of Pdx-1, MafA, intracellular ATP level, inhibiting the K-ATP current, influx of Ca2+ to the intracellular.