学术论文

      利拉鲁肽通过激活CAMKK2/AMPK通路促进骨骼肌FNDC5的表达

      Liraglutide increases FNDC5 expression in C2C12 myotubes via activa-tion of CAMKK2/AMPK signaling pathways

      摘要:
      目的:探讨利拉鲁肽(LG)对骨骼肌细胞Ⅲ型纤连蛋白结构域包含蛋白5(fibronectin typeⅢdo-main-containing protein 5,FNDC5)表达水平的影响并探讨其机制.方法:小鼠成肌细胞系C2C12经诱导分化后,给予梯度浓度(1~1000 nmol/L)LG处理不同时间(0~24 h),观察LG对FNDC5表达及磷酸化腺苷酸活化蛋白激酶(adenosine 5'-monophosphate-activated protein kinase,AMPK)信号通路活性的影响,以及应用胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)受体拮抗剂exendin9-39、钙/钙调素依赖的蛋白激酶激酶2(Ca2+/calmodulin-depen-dent protein kinase kinase 2,CAMKK2)的抑制剂STO609或AMPK的抑制剂Compound C预处理C2C12肌管细胞,观察FNDC5蛋白表达的改变.AMPK的活性及FNDC5的表达用Western blot法检测.结果:LG能够促进C2C12骨骼肌细胞FNDC5的蛋白表达,并具有剂量及时间依赖性,同时激活AMPK.LG的上述作用可被exendin9-39、STO609或Compound C阻断.结论:利拉鲁肽可促进C2C12小鼠骨骼肌细胞合成FNDC5,此作用依赖于GLP-1受体,可能是通过激活CAMKK2/AMPK信号通路实现的.
      Abstract:
      AIM:To investigate the effect of liraglutide ( LG) on the expression of fibronectin type Ⅲdomain-containing protein 5 (FNDC5) in the C2C12 myotubes.METHODS:The C2C12 mouse myoblast cell line was induced to differentiation.Differentiated cells were stimulated with gradient concentrations (1 ~1000 nmol/L) of LG for different time (0 ~24 h).The effects of LG on the expression of FNDC5 and the activation of adenosine 5'-monophosphate ( AMP)-activated protein kinase ( AMPK) signaling pathway were determined .After pretreated with glucagon-like peptide-1 ( GLP-1 ) receptor antagonist exendin 9-39 , the inhibitor of Ca 2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2), STO609, or the inhibitor of AMPK, Compound C, the LG-induced FNDC5 expression in C2C12 myotubes was examined.The expression of FNDC5 and the activation of AMPK were determined by Western blot .RESULTS: In C2C12 myotubes, LG promoted the expression of FNDC5 in a dose-and time-dependent manner .LG also activated AMPK signaling pathway .These effects of LG were partly abolished by exendin 9-39 , STO609 and Compound C .CONCLUSION:LG promotes the expression of FNDC5 via GLP-1 receptor in the C2C12 myotubes possibly through activation of the CAMKK2/AMPK signaling pathways .
      作者: 王媛妹 [1] 张玉超 [2] 陈吉翠 [3] 赵蕙琛 [2] 傅余芹 [1] 刘元涛 [2]
      Author: WANG Yuan-mei [1] ZHANG Yu-chao [2] CHEN Ji-cui [3] ZHAO Hui-chen [2] FU Yu-qin [1] LIU Yuan-tao [2]
      作者单位: 山东大学第二医院肾内科,山东济南,250031 青岛市市立医院内分泌科,山东青岛,266071 山东大学医学院细胞所,山东济南,250031
      刊 名: 中国病理生理杂志 ISTICPKU
      年,卷(期): 2017, 33(3)
      分类号: R587.1
      在线出版日期: 2017年4月10日
      基金项目: 山东省医药卫生科技发展计划