不同浓度葡萄糖对大鼠胰岛β细胞胰岛素基因表达的影响

Effect of Different Concentrations of Glucose on Insulin Gene Expression in Isolated Rat Islets

目的:研究不同浓度葡萄糖对大鼠胰岛β细胞胰岛素基因表达的影响,探讨非生理浓度葡萄糖在糖尿病发病过程中的作用。方法:用不同浓度葡萄糖分别刺激培养的胰岛β细胞1、7、14天,提取细胞总RNA,运用逆转录(RT)-PCR技术检测胰岛素基因表达的变化。结果:与对照组相比(葡萄糖浓度为5.5mmol/L),刺激胰岛β细胞1天后,葡萄糖浓度为2.2mmol/L时,胰岛素基因表达显著降低,当葡萄糖浓度高于对照组时,胰岛素基因的表达量呈浓度依赖性升高;当刺激时间为7天时,除葡萄糖浓度11.1mmol/L外,其余胰岛素基因表达均降低;如果刺激时间延长到14天,非生理浓度葡萄糖均表现为胰岛素基因的抑制作用。结论:短期的血糖升高可以一定程度地刺激胰岛素基因的表达,但长期的高血糖则表现为葡萄糖毒性作用,低血糖也可以抑制胰岛素基因的表达。

Objective: To investigate the effect of glucose on the expression of insulin gene in isolated rat islets, and study the role of non-physiological concentration of glucose in pathogenesis of diabetes mellitus. Methods: The isolated rat islets were incubated with glucose at the concentration of 2. 2 mmol/L, 5. 5 mmol/L, 11. 1 mmol/L, 16. 7 mmol/L, 33. 3 mmol/L for 1, 7, 14 days respectively. Total cellular RNA was extracted, and the expression of insulin gene was detected by RT-PCR. Results: Insulin gene expression was suppressed by glucose at the concentration of 2. 2 mmol/L compared with the controls in which glucose concentration was 5. 5 mmol/L, However, insulin gene expression were stimulated by superphysiologic concentration of glucose in a dose-dependent manner after islets were incubated with different concentrations of glucose for 1 day. Every concentration of glucose suppressed insulin gene expression except the concentration of 11. 1 mmol/L on the day 7 of incubation. When islets were stimulated as long as 14 days, all non-physiologic concentrations of glucose showed suppressive effects in insulin gene expression in a dose-dependent manner. Conclusion: Short-term exposure of isolated rat islets to superphysiologic concentration of glucose increases insulin gene expression, whereas chronic exposure exerts suppressive action, indicating the glucose toxicity on islet β cells. Insulin gene expression is reduced by un-derphysiologic concentration of glucose as well.