Yao Yanhong, Yang Xinzhou, Shen Jinhua, Zhao Ping
Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area, Institute for Medical Biology, College of Life Sciences, South-Central Minzu University, Wuhan 430074, China.
Hubei Medical Biology International Science and Technology Cooperation Base, Wuhan 430074, China.
Pharmaceuticals (Basel). 2022 Dec 25;16(1):25. doi: 10.3390/ph16010025.
GLUT4 is an important glucose transporter, which is closely related to insulin resistance and type 2 diabetes. In this study, we investigated the mechanism of Estradiol Dipropionate (EDP) on uptake of glucose in L6 skeletal muscle cells. In our study, we confirmed that EDP promoted uptake of glucose in L6 skeletal muscle cells in both normal and insulin resistant models. Western blot indicated that EDP accelerated GLUT4 expression and significantly activated AMPK and PKC phosphorylation; the expression of GLUT4 was significantly inhibited by AMPK inhibitor compound C and PKC inhibitor Gö6983, but not by Wortmannin (Akt inhibitor). Meanwhile, EDP boosted GLUT4 expression, and also increased intracellular Ca levels. In the presence of 2 mM, 0 mM extracellular Ca and 0 mM extracellular Ca + BAPTA-AM, the involvement of intracellular Ca levels contribute to EDP-induced GLUT4 expression and fusion with plasma membrane. Therefore, this study investigated whether EDP promoted GLUT4 expression through AMPK and PKC signaling pathways, thereby enhancing GLUT4 uptake of glucose and fusion into plasma membrane in L6 skeletal muscle cells. In addition, both EDP induced GLUT4 translocation and uptake of glucose were Ca dependent. These findings suggested that EDP may be potential drug for the treatment of type 2 diabetes.
葡萄糖转运蛋白4(GLUT4)是一种重要的葡萄糖转运体,与胰岛素抵抗和2型糖尿病密切相关。在本研究中,我们探究了二丙酸雌二醇(EDP)对L6骨骼肌细胞摄取葡萄糖的作用机制。在我们的研究中,我们证实EDP在正常和胰岛素抵抗模型中均能促进L6骨骼肌细胞摄取葡萄糖。蛋白质免疫印迹法表明,EDP能加速GLUT4的表达,并显著激活AMPK和PKC的磷酸化;AMPK抑制剂化合物C和PKC抑制剂Gö6983能显著抑制GLUT4的表达,但渥曼青霉素(Akt抑制剂)则无此作用。同时,EDP能促进GLUT4的表达,还能提高细胞内钙离子水平。在细胞外钙离子浓度为2 mM、0 mM以及0 mM细胞外钙离子+ BAPTA-AM的情况下,细胞内钙离子水平参与了EDP诱导的GLUT4表达以及与质膜的融合过程。因此,本研究探究了EDP是否通过AMPK和PKC信号通路促进GLUT4的表达,从而增强L6骨骼肌细胞对葡萄糖的摄取以及GLUT4与质膜的融合。此外,EDP诱导的GLUT4转位和葡萄糖摄取均依赖钙离子。这些研究结果表明,EDP可能是治疗2型糖尿病的潜在药物。