title: Differential effect of insulin and elevated glucose level on adenosine handling in rat T lymphocytes.
abstract: Reduced proliferation potential is among other T cell functional defects long known feature of diabetes. However, the mechanism responsible for this impairment is still unknown. Our study was undertaken to investigate the effect of changes in glucose and insulin concentrations on adenosine metabolism, transport and receptor-mediated action in rat T lymphocytes. Presented results indicate that vulnerability of T cells to metabolic stress is determined by insulin but not by glucose concentration. However, glucose and insulin differentially affected the activities of adenosine metabolizing enzymes in resting and proliferating T cells. The Con A-induced proliferation of cultured T lymphocytes did not depended on expression level and functional state of nucleoside transporters. Inhibition of adenosine kinase (AK) with 5-iodotubercidin lowers the proliferation potential of T cells to the level observed for insulin-deprived cells. Moreover, insulin-deprived T lymphocytes but not cells cultured in the presence of insulin released significant quantities of adenosine. Under resting conditions, the cAMP level was fivefold higher in cells deprived of insulin comparing to cells cultured in the presence of insulin. Exposition of insulin-deprived T lymphocytes to specific antagonist (ZM241385) of A2a receptor but not to specific antagonist (Alloxazine) of A2b receptor suppressed cAMP elevation and completely restored the proliferation potential of T cells. Concluding, adenosine released by insulin-deprived T cells due to suppressed AK activity by acting on A2a receptors leads to increases in cAMP level and suppression of T cell proliferation. We assume that this mechanism may significantly contribute to immune impairment observed in diabetes.
authors.affiliation: Department of Molecular Medicine, Medical University of Gdansk, 80-211 Gdansk, Poland. tkpaw@amg.gda.pl
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pawelczyk
authors.forename: Monika
authors.initials: M
authors.lastname: Sakowicz-Burkiewicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kocbuch
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szutowicz
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000248:Adenosine Kinase / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011684:Purine Nucleosides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D007328:Insulin; D011684:Purine Nucleosides; D018047:Receptors, Purinergic P1; D003208:Concanavalin A; D000255:Adenosine Triphosphate; D000248:Adenosine Kinase; D005947:Glucose; D000241:Adenosine