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龙血素B通过GLP-1R和AKT/PDX1途径促进胰岛素分泌。

Loureirin B promotes insulin secretion through GLP-1R and AKT/PDX1 pathways.

作者信息

Fang Haowen, Ding Yanting, Xia Sijing, Chen Qin, Niu Bing

机构信息

Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, PR China.

Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, PR China; Shanghai Biochip Co., Ltd., National Engineering Center for Biochip at Shanghai, Shanghai, PR China.

出版信息

Eur J Pharmacol. 2022 Dec 5;936:175377. doi: 10.1016/j.ejphar.2022.175377. Epub 2022 Nov 5.

Abstract

Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated a diabetic model in mice with LB, and the results showed that LB lowered blood glucose and alleviated islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated mice with LB in a diabetic model and showed that LB lowered blood glucose and reduced islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Further, after inhibiting GLP-1R activity, the results showed that LB promoted insulin secretion, Ins-1 cell proliferation and reduced Ins-1 cell apoptosis with reduced effect, indicating that LB achieved the above effects by activating GLP-1Ra. Meanwhile, cellular cAMP levels increased when GLP-1R was overexpressed, which also demonstrated the interaction between LB and GLP-1R. Subsequently, the effect of LB on cellular potassium channels was examined by membrane clamp, and the results showed that LB increased intracellular Ca concentration and stimulated insulin secretion by activating GLP-1R and thus closing the ATP-sensitive potassium channels. On the other hand, the activation effect of LB on AKT/PDX1 signaling pathway was verified.

摘要

龙血素B(LB)是一种从血竭中提取的天然产物,对糖尿病小鼠具有降血糖作用。然而,关于LB如何降低血糖尚无研究。在本研究中,我们首先用LB处理小鼠糖尿病模型,结果表明LB可降低小鼠血糖并减轻胰岛损伤。接下来,用LB处理胰岛β-1(Ins-1)细胞。结果表明,LB可促进Ins-1细胞增殖并减少其凋亡。龙血素B(LB)是一种从血竭中提取的天然产物,对糖尿病小鼠具有降血糖作用。然而,关于LB如何降低血糖尚无研究。在本研究中,我们首先在糖尿病模型中用LB处理小鼠,结果表明LB可降低小鼠血糖并减少胰岛损伤。接下来,用LB处理Ins-1细胞。结果表明,LB可促进细胞增殖并减少Ins-1细胞凋亡。此外,抑制胰高血糖素样肽-1受体(GLP-1R)活性后,结果显示LB促进胰岛素分泌、Ins-1细胞增殖并减少Ins-1细胞凋亡,但作用减弱,表明LB通过激活GLP-1Rα发挥上述作用。同时,GLP-1R过表达时细胞内环磷酸腺苷(cAMP)水平升高,这也证明了LB与GLP-1R之间的相互作用。随后,通过膜片钳检测LB对细胞钾通道的影响,结果表明LB通过激活GLP-1R增加细胞内钙离子浓度并刺激胰岛素分泌,从而关闭ATP敏感性钾通道。另一方面,验证了LB对AKT/胰腺十二指肠同源盒-1(PDX1)信号通路的激活作用。

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