C2C12 Skeletal Muscle Cells Exposure to Phosphatidylcholine Triggers IGF-1 Like-Responses

C2C12 Skeletal Muscle Cells Exposure to Phosphatidylcholine Triggers IGF-1 Like-Responses
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C2C12 骨骼肌细胞暴露于磷脂酰胆碱会触发 IGF-1 样反应

DOI:
10.1159/000086408
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发表时间:
2005
影响因子:
--
通讯作者:
P. Loughna
P. Loughna
中科院分区:
医学1区
文献类型:
--
作者:
C. Rauch;P. Loughna

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细胞对IGF-1或胰岛素刺激的葡萄糖摄取与GLUT(葡萄糖转运蛋白)蛋白从细胞内细胞质区室到质膜的易位有关。响应于这样的刺激,GLUT 4和GLUT 1向质膜的易位通过其胞吐作用的增加而触发,所述胞吐作用涉及磷脂酶D(PLD)活化,破坏细胞内含有GLUT的囊泡在质膜和内部隔室之间的再循环。在骨骼肌中,观察到胰岛素抵抗与二棕榈酰磷脂酰胆碱的增加相关,二棕榈酰磷脂酰胆碱也已知与PLD相互作用。基于证据表明,循环过程是重要的GLUT易位,我们决定解决是否二棕榈酰磷脂酰胆碱,一个不可转位的磷脂已知改变细胞内囊泡的再循环,并与PLD相互作用,可以参与葡萄糖代谢。我们发现,通过添加二棕榈酰-磷脂酰胆碱,磷脂组成的急剧变化导致GLUT 1易位至质膜,同时Akt和GSK 3 β磷酸化增加,这对PI 3 K和PLD抑制剂敏感。此外,我们还表明,长期变化的磷脂组成破坏了IGF-1信号通路和GLUT 1分配在细胞内。
Glucose uptake by cells in response to stimulation with either IGF-1 or insulin is associated with the translocation of GLUT (glucose transporter) proteins from intracellular cytoplasmic compartments to the plasma membrane. In response to such stimulation, GLUT4 and GLUT1 translocation to the plasma membrane is triggered through an increase in their exocytosis involving phospholipase D (PLD) activation, disrupting the recycling of intracellular GLUT-containing vesicles between the plasma membrane and internal compartments. In skeletal muscle, insulin resistance is observed in association with an increase of dipalmitoyl-phosphatidylcholine, which is also known to interact with PLD. Based on evidence that the recycling process is important for GLUT translocation, we decided to address whether dipalmitoyl-phosphatidylcholine, a non-translocatable phospholipid known to alter the recycling of intracellular vesicles and to interact with PLD, can be involved in glucose metabolism. We show that an acute change in phospholipid composition, by addition of dipalmitoyl-phophatidylcholine, leads to GLUT1 translocation to the plasma membrane in conjunction to an increase of Akt and GSK3β phosphorylation, which are sensitive to PI3K and PLD inhibitors. Moreover, we also show that long-term change in phospholipid composition disrupts both the IGF-1 signalling pathway and GLUT1 partitioning within the cells.
DOI: 10.1016/j.ymeth.2004.01.002
发表时间: 2004-08-01
期刊: METHODS
影响因子: 4.8
作者:
Brumback, AC;Lieber, JL;Betz, WJ
通讯作者: Betz, WJ
DOI: --
发表时间: 1988
期刊: The Journal of biological chemistry
影响因子: --
作者:
Calderhead,DM;Lienhard,GE
通讯作者: Lienhard,GE