过表达KLF4对棕榈酸所致L6骨骼肌细胞胰岛素抵抗的影响
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摘要
目的探讨Krüppel样因子4(KLF4)过表达对大鼠L6骨骼肌细胞胰岛素抵抗的影响。方法采用棕榈酸诱导法建立大鼠L6骨骼肌细胞的胰岛素抵抗模型,随机分为对照组和转染组。对照组转染腺病毒空载体(Ad),转染组转染KLF4腺病毒表达载体(Ad-KLF4)。采用Real-time PCR和Western-blot检测两组KLF4、胰岛素受体(IR)和葡萄糖转运蛋白4(GLUT4)的表达水平,采用葡萄糖氧化酶法检测两组培养液中的葡萄糖浓度。结果与对照组比较,棕榈酸诱导组对葡萄糖的摄取量显著降低(P<0.05),KLF4、IR、GLUT4表达显著下调(P<0.05)。KLF4过表达可显著提高细胞对胰岛素的敏感性,并上调IR、GLUT4表达。结论过表达KLF4可导致IR、GLUT4表达上调,并改善骨骼肌细胞的胰岛素抵抗。
Objective To investigate the effect of Krüppel-like factor 4( KLF4) overexpression on palmitate-induced insulin resistance in L6 skeleton muscle cells of rats. Methods The insulin resistance models in L6 skeleton muscle cells of rats were induced by palmitic acid,which were randomly divided into two groups,control group and experiment group. The differentiated L6 skeleton muscle cells in control group were transfected with adenovirus empty vector( Ad),however,which in experiment group were transfected with KLF4 adenovirus expression vector( Ad-KLF4). The expression levels of KLF4,insulin receptor( IR) and glucose transporter type 4( GLUT4) in both groups were detected by Real-time PCR and Western Blot. Results As compared to those in control group,the expression levels of KLF4,IR and GLUT4 in experiment group were significantly down-regulated( P < 0. 05),and the intaking amount for glucose was obviously decreased( P < 0. 05). The overexpression of KLF4 could enhance the sensitivities of the cells to insulin,and could up-regulate the expression levels of IR and GLUT4. Conclusion KLF4 overexpression can up-regulate the expression levels of IR and GLUT4,and can improve insulin sensitivities of L6 cells effectively.
Objective To investigate the effect of Krüppel-like factor 4( KLF4) overexpression on palmitate-induced insulin resistance in L6 skeleton muscle cells of rats. Methods The insulin resistance models in L6 skeleton muscle cells of rats were induced by palmitic acid,which were randomly divided into two groups,control group and experiment group. The differentiated L6 skeleton muscle cells in control group were transfected with adenovirus empty vector( Ad),however,which in experiment group were transfected with KLF4 adenovirus expression vector( Ad-KLF4). The expression levels of KLF4,insulin receptor( IR) and glucose transporter type 4( GLUT4) in both groups were detected by Real-time PCR and Western Blot. Results As compared to those in control group,the expression levels of KLF4,IR and GLUT4 in experiment group were significantly down-regulated( P < 0. 05),and the intaking amount for glucose was obviously decreased( P < 0. 05). The overexpression of KLF4 could enhance the sensitivities of the cells to insulin,and could up-regulate the expression levels of IR and GLUT4. Conclusion KLF4 overexpression can up-regulate the expression levels of IR and GLUT4,and can improve insulin sensitivities of L6 cells effectively.
引文
1 Lipina C,Macrae K,Suhm T,et al.Mitochondrial substrate availability and its role in lipid-induced insulin resistance and proinflammatorysignalingin skeletal muscle.Diabetes,2013,62:3426-3436.
2 Lin ZS,Chu HC,Yen YC,et al.Krüppel-like factor 4,a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression.PLoS One,2012,7:43593.
3 Aktug H,Uysal A,Yavasoglu A,et al.The detrimental effects ofdiabeteson pluripotency determined byKLF4,SOX2,C-MYC and OCT4 immunoreactivity in rat testes.Adv Clin Exp Med,2013,22:327-335.
4 Evans PM,Liu C.Roles of Krüpel-like factor 4 in normal homeostasis,cancer and stem cells.ActaBiochimBiophys Sin,2008,40:554-564.
5 Rui ZH,Mei HA,Bin ZH,et al.Krüppel-like factor 4 interacts with p300to activate mitofusin 2 gene expression induced by all-transretinoic acid in VSMCs.ActaPharmacologica Sinica,2010,31:1293-1302.
6 Evans PM,Zhang W,Chen X,et al.Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation.J Biol Chem,2007,282:33994-34002.
2 Lin ZS,Chu HC,Yen YC,et al.Krüppel-like factor 4,a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression.PLoS One,2012,7:43593.
3 Aktug H,Uysal A,Yavasoglu A,et al.The detrimental effects ofdiabeteson pluripotency determined byKLF4,SOX2,C-MYC and OCT4 immunoreactivity in rat testes.Adv Clin Exp Med,2013,22:327-335.
4 Evans PM,Liu C.Roles of Krüpel-like factor 4 in normal homeostasis,cancer and stem cells.ActaBiochimBiophys Sin,2008,40:554-564.
5 Rui ZH,Mei HA,Bin ZH,et al.Krüppel-like factor 4 interacts with p300to activate mitofusin 2 gene expression induced by all-transretinoic acid in VSMCs.ActaPharmacologica Sinica,2010,31:1293-1302.
6 Evans PM,Zhang W,Chen X,et al.Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation.J Biol Chem,2007,282:33994-34002.