Effect of hyperglycemia on the basal cytosolic free calcium level, calcium signal and tyrosine-phosphorylation in human T-cells.

In this study, we investigated the effect of in vitro hyperglycemia on the function of human T-cells (Jurkat cells). Hyperglycemic conditions caused concentration-dependent elevation of basal cytosolic free calcium level and reduced calcium signal (activation capacity), either after ionomycin or monoclonal anti-CD3 antibody treatments. Similar changes were observed if cells were treated with the calcineurin inhibitor Cyclosporin-A. We found that tyrosine-phosphorylation after anti-CD3 treatment was also impaired. High glucose concentrations in the tissue culture medium are also associated with increased non-enzymatic glycation of T-cell proteins. We propose that the increased glycation of proteins involved in calcium transport and/or intracellular signal transduction in T-cells accounts for the abnormal calcium sequestration and calcium mediated signal transduction.