Insulin and glucose induced changes in expression level of nucleoside transporters and adenosine transport in rat T lymphocytes

• Published in: Biochemical pharmacology 2004-10, Vol.68 (7), p.1309-1320
• Main Authors: Sakowicz, Monika, Szutowicz, Andrzej, Pawelczyk, Tadeusz
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine - metabolism; Animals; Biological and medical sciences; Biological Transport - drug effects; Gene Expression - drug effects; Glucose; Glucose - pharmacology; Insulin; Insulin - pharmacology; Male; Medical sciences; Nucleoside Transport Proteins - genetics; Nucleoside Transport Proteins - metabolism; Nucleoside transporters; Pharmacology. Drug treatments; Rats; Rats, Wistar; T lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism
• ISSN: 0006-2952; 1873-2968
• 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 10 nM 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 (20 mM) and low (5 mM) 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.