转化生长因子-β对大鼠胰岛素基因表达的调节作用

Tansforming growth factor-β regulates insulin gene expression in isolated rat islets

目的:研究不同浓度转化生长因子-β(TGF-β)对大鼠胰岛细胞胰岛素基因表达的影响,探讨TGF-β在2型糖尿病治疗中的作用。方法:大鼠胰岛细胞与不同刺激浓度的TGF-β(0ng/mL、1ng/mL、2ng/mL、5ng/mL、10ng/mL、20ng/mL)和葡萄糖浓度分别为2.2mmol/L、5.5mmol/L、11.1mmol/L的RPMI1640营养液共培养24h后,提取细胞总RNA。运用RT-PCR技术检测胰岛素基因表达的变化。结果:葡萄糖浓度为2.2mmol/L时,随TGF-β浓度逐渐升高,胰岛素基因表达量无明显变化;葡萄糖浓度为5.5mmol/L时,TGF-β浓度由0ng/mL升至2ng/mL时,胰岛素基因表达量无变化,而当TGF-β浓度进一步升高,胰岛素基因表达量呈剂量依赖性升高;葡萄糖浓度为11.1mmol/L时,随TGF-β浓度升高,胰岛素基因表达量呈浓度依赖性升高。结论:TGF-β以葡萄糖依赖和浓度依赖方式促进胰岛素基因的表达。

Objective：To investigate the effect of tansforming growth factor-β（TGF-β） on insulin gene expression in isolated rat islets, and to study the role of TGF-β in the treatment of type 2 diabetes mellitus. Methods： TGF-β was added to isolated islets at the final concentrations of 0, 1,2,5, 10, and 20ng/mL to RPMI1640 medium containing 2.2mmol/L （low）, 5.5mmol/L （normal） and 11. lmmol/L （high） glucose. All islet samples were harvested after incubation for 24h, and total RNA was extracted from RPMI1640 medium for RT-PCR. Results： When glucose level was 2.2mmol/L, no change occurred in insulin gene expression at different concentrations of TGF-β The low and normal physiologic concentrations of TGF-β had no effect on insulin gene expression at the glucose level of 5.5mmol/L. In contrast, physiologic concentrations of TGF-β stimulated insulin gene expression in a dose-dependent manner. The insulin mRNA levels were higher at the glucose level of 11. I mmol/L. Conclusion： TGF-β up-regulates insulin mRNA level in a glucose concentration-dependent manner.