葡萄糖对胰岛细胞胰腺-十二指肠同源盒基因-1表达的影响

Effect of glucose on PDX-1 gene expression in isolated rat islet cells

目的研究不同浓度葡萄糖对大鼠胰岛细胞胰腺-十二指肠同源盒基因-1(PDX-1)表达的调节作用。方法用不同浓度葡萄糖分别刺激胰岛细胞1、4、7、14d,运用RT-PCR技术检测PDX-1基因表达的变化。结果与对照组相比(葡萄糖浓度为5.5mmol/L),刺激胰岛细胞1d时,葡萄糖浓度为2.2mmol/L时,PDX-1表达显著降低,当葡萄糖浓度高于对照组时,PDX-1基因的表达量呈浓度依赖性升高;4d时,低糖浓度仍然显著抑制PDX-1基因表达,浓度升至11.1mmol/L,PDX-1基因表达量呈显著升高,浓度为16.7mmol/L时,PDX-1基因表达量呈下降趋势,浓度升至33.3mmol/L时,PDX-1基因表达量明显降低;7d时,除浓度11.1mmol/L外,其余浓度PDX-1基因表达均降低;刺激时间延长到14d,非生理浓度葡萄糖均表现为对PDX-1基因的抑制作用。结论低血糖可以抑制PDX-1基因表达。短期的血糖升高可以一定程度地刺激PDX-1基因表达,但长期的高血糖则使PDX-1基因表达明显受抑。

Objective To investigate the effect of glucose on the expression of PDX-1 gene in isolated rat islets. Methods The isolated rat islets were incubated with different concentrations of glucose for 1, 4, 7 and 14 days, The expression of PDX-1 gene was detected by RT-PCR. Results Compared with normal glucose concentration （5.5 mmol/L）, PDX-1 gene expression was suppressed by glucose of 2.2 mmol/L, while the gene expression was stimulated by higher concentrations of glucose in a dose-dependent manner on the 1st day. After incubation for 4 days, PDX-1 gene expression was suppressed significantly by glucose of 2. 2 mmol/L. PDX-1 gene expression was stimulated by glucose of 11.1 mmol/L, whereas there was a down tenotency in PDX-1 mRNA with 16.7 mmol/L glucose, though PDX-1 mRNA was suppressed by 33.3 mmol/L glucose significantly. After 7 days incubation with glucose, PDX-1 gene expressions were suppressed markedly in various concentrations except for 11.1 mmol/L. When islets were incubated with glucose as long as 14 days, all non-physiological concentrations of glucose possessed suppressive effect on PDX-1 gene expression in a dose-dependent manner. Conclusions PDX-1 gene expression is reduced by lower than normal glucose concentration. Short-term exposure of isolated rat islets to supraphysiologic concentration of glucose increases PDX-1 gene expression, while chronic exposure exerts suppressive action, suggesting the glucose toxicity on β cells.