Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats
Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats
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DOI：
10.1016/j.neulet.2009.09.012
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发表时间：
2009-11-20
影响因子：
2.5
通讯作者：
Cheng, Juei-Tang
中科院分区：
文献类型：
--
作者：
Cheng, Tse-Chou;Lin, Chian-Shiung;Cheng, Juei-Tang
姜黄素是姜黄根茎中含有的一种活性成分，据称通过其抗氧化和抗炎特性对糖尿病有治疗作用。在本研究中，我们发现姜黄素导致 Wistar 大鼠骨骼肌葡萄糖摄取量呈浓度依赖性增加。这种作用被浓度足以阻断毒蕈碱 M-1 胆碱受体 (M-1-mAChR) 的哌仑西平抑制。在放射性配体结合测定中，[H-3]-哌仑西平的结合也以浓度依赖性方式被姜黄素取代。在 PLC-PI3K 通路抑制剂 U73122（磷脂酶 C 抑制剂）或 LY294002（磷酸肌醇 3-激酶抑制剂）存在的情况下，姜黄素刺激的骨骼肌葡萄糖摄取显着减少。在蛋白质印迹分析中，姜黄素增加的葡萄糖转运蛋白4（GLUT4）的膜蛋白水平也通过以相同的方式阻断M-1-mAChR或PLC-PI3K途径而逆转。总之，所获得的结果表明姜黄素可以在低于浓度的情况下激活M1-mAChR以清除自由基，从而通过PLC-PI3激酶途径增加骨骼肌对葡萄糖的摄取。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M-1-mAChR) In radioligand binding assay, the binding of [H-3]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M-1-mAChR or PLC-PI3K pathway in a same manner In conclusion, the obtained results Suggest that curcumin can activate M1-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.