Sakowicz Monika, Szutowicz Andrzej, Pawelczyk Tadeusz
Department of Molecular Medicine, Medical University of Gdansk, Poland.
Biochem Pharmacol. 2004 Oct 1;68(7):1309-20. doi: 10.1016/j.bcp.2004.06.020.
Adenosine is an endogenous agent exerting potent action on the immune system including regulation of lymphocyte functioning. Impaired T lymphocyte functioning is a common feature of diabetes. The aims of this study were to examine the effects of glucose and insulin on nucleoside transporters (NT) expression level and adenosine (Ado) transport in rat T lymphocytes cultured under the defined concentrations of glucose and insulin. Performed experiments revealed that rat T lymphocytes expressed the equilibrative nucleoside transporter type 1 and 2 (rENT1, rENT2) and concentrative nucleoside transporter type 2 (rCNT2). The mRNA levels of rENT2 and rCNT2 were highly dependent on insulin but were not affected by changes in extracellular glucose concentration. Exposition of T cells to 10nM insulin resulted in 73% increase in rENT2 mRNA and 50% decrease in the rCNT2 mRNA level. The level of rENT1 mRNA was sensitive to extracellular glucose concentration but not to insulin. The highest differences among cells cultured in high (20mM) and low (5mM) glucose were observed in equilibrative nitrobenzylthioinosine sensitive adenosine transport, which was lowered by 65% in cells cultured at high glucose. Alterations in adenosine transport were accompanied by changes in adenosine accumulation in the cell. These results indicate that adenosine transport in rat T lymphocytes is independently and differentially regulated by glucose and insulin by means of changes in the nucleoside transporters expression level. Altered adenosine transport has a great impact on its intracellular level. This suggests that under diabetic conditions adenosine action on T lymphocytes might be altered.
腺苷是一种内源性物质，对免疫系统具有强大作用，包括调节淋巴细胞功能。T淋巴细胞功能受损是糖尿病的一个常见特征。本研究的目的是检测葡萄糖和胰岛素对在特定浓度葡萄糖和胰岛素条件下培养的大鼠T淋巴细胞中核苷转运体（NT）表达水平和腺苷（Ado）转运的影响。所进行的实验表明，大鼠T淋巴细胞表达1型和2型平衡核苷转运体（rENT1、rENT2）以及2型浓缩核苷转运体（rCNT2）。rENT2和rCNT2的mRNA水平高度依赖胰岛素，但不受细胞外葡萄糖浓度变化的影响。将T细胞暴露于10nM胰岛素中会导致rENT2 mRNA增加73%，rCNT2 mRNA水平降低50%。rENT1 mRNA水平对细胞外葡萄糖浓度敏感，但对胰岛素不敏感。在高（20mM）葡萄糖和低（5mM）葡萄糖条件下培养的细胞中，在平衡型硫代硝基苯甲酰基肌苷敏感的腺苷转运方面观察到最大差异，在高葡萄糖条件下培养的细胞中该转运降低了65%。腺苷转运的改变伴随着细胞内腺苷积累的变化。这些结果表明，大鼠T淋巴细胞中的腺苷转运通过核苷转运体表达水平的变化受到葡萄糖和胰岛素的独立且不同的调节。腺苷转运的改变对其细胞内水平有很大影响。这表明在糖尿病条件下，腺苷对T淋巴细胞的作用可能会改变。
