A natural compound jaceosidin ameliorates endoplasmic reticulum stress and insulin resistance via upregulation of SERCA2b
A natural compound jaceosidin ameliorates endoplasmic reticulum stress and insulin resistance via upregulation of SERCA2b
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天然化合物 jaceosidin 通过上调 SERCA2b 改善内质网应激和胰岛素抵抗
DOI：
10.1016/j.biopha.2017.03.023
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发表时间：
2017-05-01
影响因子：
7.5
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Ouyang, Zijun;Li, Wanshuai;Xu, Qiang
内质网（ER）应激的增加是葡萄糖稳态失调的重要原因，而肌质内质网Ca~（2+）-ATP酶2b（SERCA2b）功能受损是ER应激的重要机制之一。在这项研究中，我们报道了SERCA2b上调有助于改善ER应激和胰岛素抵抗的小天然化合物jaceosidin。在分化的C2C12肌管模型中，jaceosidin触发的SERCA2b上调增强胰岛素敏感性并降低ER应激。此外，在毒扁豆碱处理的肌管中的Ca~（2+）-ATP酶的活性也被jaceosidin增强。此外，jaceosidin显着抑制血糖水平，改善葡萄糖耐量和降低体重，但不改变胰岛素抵抗肥胖小鼠的食物摄入量。此外，该化合物还能显著降低脂质蓄积，抑制肝脏中脂肪生成基因的表达，改善肝损伤。jaceosidin的改善作用是由于其通过增加肥胖小鼠肌肉中SERCA2b的表达来减少ER应激的能力。综上所述，jaceosidin可以通过上调小鼠骨骼肌中SERCA2b来改善ER应激并减轻胰岛素抵抗。(C)2017年Elsevier Masson SAS。All rights reserved.
Increased endoplasmic reticulum (ER) stress has emerged as a vital contributor to dysregulated glucose homeostasis, and impaired function of sarco-endoplasmic reticulum Ca2+-ATPase 2b ( SERCA2b) is one of the central mechanisms underlying ER stress. In this study, we reported that SERCA2b upregulation contributed to the amelioration of ER stress and insulin resistance by a small natural compound jaceosidin. In a model of differentiated C2C12 myotubes, jaceosidin-triggered SERCA2b upregulation enhanced insulin sensitivity and decreased ER stress. Moreover, the activity of Ca2+-ATPase in thapsigargin-treated myotubes was also augmented by jaceosidin. Furthermore, jaceosidin significantly suppressed blood glucose levels, improved glucose tolerance and lowered body weight, but did not alter food intake in insulin-resistant obese mice. In addition, this compound markedly reduced lipid accumulation, suppressed the expression of lipogenic genes in liver and ameliorated liver injury. The ameliorative effects of jaceosidin were due to its ability to reduce ER stress via increasing the expression of SERCA2b in the muscles of obese mice. Taken together, jaceosidin could improve ER stress and attenuate insulin resistance via SERCA2b upregulation in mice skeletal muscles. (C) 2017 Elsevier Masson SAS. All rights reserved.