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目的探讨雄激素对胰岛素敏感性影响的可能的分子机制。方法诱导3T3-L1前脂肪细胞系和C2C12成肌细胞系分别分化为3T3-L1脂肪细胞和C2C12骨骼肌细胞,然后对这两种细胞分别以10-9mol/L睾酮处理4、8、12、24及48h,并以不同浓度(10-12~10-5mol/L)的睾酮处理24h,用Western印迹的方法检测两种细胞在以两种方法处理后胰岛素受体底物1(IRS-1)和葡萄糖转运载体4(GLUT4)表达的变化。结果随着10-9mol/L浓度的睾酮处理时间的延长,IRS-1和GLUT4在两种细胞的表达逐渐增加,IRS-1于12h达峰后下降。3T3-L1脂肪细胞及C2C12骨骼肌细胞中12h峰值分别是0h对照的(1·42±0·42)倍和(1·53±0·14)倍,均P<0·05;GLUT4于24h达峰后表达下降[3T3-L1脂肪细胞及C2C12骨骼肌细胞中24h峰值分别是0h的(3·22±0·10)倍和(5·17±1·06)倍,均P<0·05]。当睾酮处理浓度从10-12mol/L逐渐增加时,IRS-1在两种细胞的表达逐渐增加,于10-9mol/L达峰值后表达逐渐下降[在3T3-L1脂肪细胞和C2C12骨骼肌细胞,10-9mol/L睾酮处理后的峰值较空白对照分别增加(4·23±0·27)倍和(3·16±0·15)倍,均P<0·05]。GLUT4在C2C12骨骼肌细胞的表达随着睾酮浓度的升高有增加的趋势[经10-7mol/L睾酮处理后的表达量是空白对照的(2·99±0·15)倍,P<0·05,于10-7mol/L后增加趋势不明显。在3T3-L1脂肪细胞中,GLUT4的表达于10-11mol/L达峰值[较空白对照增加(2·58±0·02)倍,P<0·05],然后随着睾酮浓度的升高表达下降。结论睾酮影响胰岛素信号转导分子的表达存在剂量和时间上的双向作用。
Objective To investigate the possible molecular mechanism of androgen sensitivity to insulin. Methods The 3T3-L1 preadipocytes and C2C12 myoblasts were induced to differentiate into 3T3-L1 adipocytes and C2C12 skeletal muscle cells, respectively. The cells were treated with 10-9mol / L testosterone for 4, 8, 24 and 48h, respectively, and treated with different concentrations (10-12 ~ 10-5mol / L) of testosterone for 24 hours. Western blotting was used to detect the expression of insulin receptor substrate 1 (IRS-1 ) And glucose transporter 4 (GLUT4) expression changes. Results The expression of IRS-1 and GLUT4 in both cell lines increased gradually with the time of 10-9 mol / L testosterone treatment, and IRS-1 decreased after reaching the peak at 12h. The peak values of 12h in 3T3-L1 adipocytes and C2C12 skeletal muscle cells were (1.42 ± 0.42) times and (1.53 ± 0.14) times of 0h control, respectively, P <0.05; The peak of 24h in 3T3-L1 adipocytes and C2C12 skeletal muscle cells was (3 · 22 ± 0.10) times and (5 · 17 ± 1 · 06) times of 0h respectively, all P <0 · 05]. When the concentration of testosterone gradually increased from 10-12mol / L, the expression of IRS-1 gradually increased in both cells, and gradually decreased after the peak of 10-9mol / L [in 3T3-L1 adipocytes and C2C12 skeletal muscle cells (P <0.05). The peak value of 10-9mol / L testosterone increased (4.23 ± 0.27) times and (3.16 ± 0.15) times, respectively, compared with the blank control group (P <0.05). The expression of GLUT4 in C2C12 skeletal muscle cells increased with the increase of testosterone concentration (2.99 ± 0.15 times) after 10-7mol / L testosterone treatment, P <0 · 05, after 10-7mol / L increased trend is not obvious. In 3T3-L1 adipocytes, the expression of GLUT4 peaked at 10-11mol / L (2.58 ± 0.02 times the blank control, P <0.05), and then increased with the increase of testosterone Decreased expression. Conclusion Testosterone has a dose-and-time bidirectional effect on the expression of insulin signaling molecules.