Palmitic acid acutely stimulates glucose uptake via activation of Akt and ERK1/2 in skeletal muscle cells
Palmitic acid acutely stimulates glucose uptake via activation of Akt and ERK1/2 in skeletal muscle cells
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DOI：
10.1194/jlr.m011254
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发表时间：
2011-07-01
影响因子：
6.5
通讯作者：
Liu, Pingsheng
中科院分区：
文献类型：
--
作者：
Pu, Jing;Peng, Gong;Liu, Pingsheng
长期接触饱和脂肪酸会导致胰岛素抵抗。然而，脂肪酸的急性效应尚不清楚，需要阐明，因为血浆脂肪酸浓度波动餐后。在这里，我们提出了棕榈酸（PA）对骨骼肌细胞的急性效应及其潜在的分子机制。免疫荧光结果表明，PA可迅速诱导大鼠骨骼肌细胞L 6的GLUT 4易位，并刺激葡萄糖摄取。PA以时间依赖性方式增强AMP活化蛋白激酶（AMPK）、Akt和细胞外信号相关激酶1/2（ERK 1/2）的磷酸化。细胞表面结合的PA足以刺激Akt磷酸化。PI 3激酶（PI 3 K）、AMPK、Akt和ERK 1/2抑制剂可降低PA诱导的葡萄糖摄取，PI 3 K抑制剂可降低AMPK、Akt和ERK 1/2磷酸化水平。AMPK活性减弱可降低Akt的磷酸化水平，但对ERK 1/2无影响，Akt抑制剂对ERK 1/2活性无影响。ERK 1/2抑制剂对Akt磷酸化无影响。综上所述，我们的数据表明，PA介导的骨骼肌细胞葡萄糖摄取可能是通过PA与细胞表面的结合刺激的，随后是独立的PI 3 K/AMPK/Akt和PI 3 K/ERK 1/2途径。Pu，J.，G.彭湖，澳-地Li，H. Na，Y. Liu和P. Liu。软脂酸通过激活骨骼肌细胞中的Akt和ERK 1/2来急性刺激葡萄糖摄取。J. Lipid Res. 2011。52：1319-1327。
Chronic exposure to saturated fatty acids can cause insulin resistance. However, the acute effects of fatty acids are not clear and need to be elucidated because plasma fatty acid concentrations fluctuate postprandially. Here, we present the acute effects of palmitate (PA) on skeletal muscle cells and their underlying molecular mechanisms. Immunofluorescence results showed that PA rapidly induced GLUT4 translocation and stimulated glucose uptake in rat skeletal muscle cell line L6. Phosphorylation of AMP-activated protein kinase (AMPK), Akt, and extracellular signal-related kinase1/2 (ERK1/2) was enhanced by PA in a time-dependent manner. Cell surface-bound PA was sufficient to stimulate Akt phosphorylation. The inhibitors of PI3 kinase (PI3K), AMPK, Akt, and ERK1/2 could decrease PA-induced glucose uptake, and PI3K inhibitor decreased AMPK, Akt, and ERK1/2 phosphorylation. Weakening AMPK activity reduced phosphorylation of Akt but not ERK1/2, and Akt inhibitor could not affect ERK1/2 activation either. Meanwhile, ERK1/2 inhibitors had no effect on Akt phosphorylation. Taken together, our data suggest that PA-mediated glucose uptake in skeletal muscle cells may be stimulated by the binding of PA to cell surface and followed by PI3K/AMPK/Akt and PI3K/ERK1/2 pathways independently.-Pu, J., G. Peng, L. Li, H. Na, Y. Liu, and P. Liu. Palmitic acid acutely stimulates glucose uptake via activation of Akt and ERK1/2 in skeletal muscle cells. J. Lipid Res. 2011. 52: 1319-1327.