Experimental diabetes attenuates calcium mobilization and proliferative response in splenic lymphocytes from mice.

The present study was conducted to investigate the effects of the diabetic condition on cytosolic free Ca(2+) concentration, Ca(2+), and the proliferation of splenic lymphocytes from mice. Diabetes was induced in mice by intraperitoneal injection of alloxan. Ca(2+) and the proliferation ex vivo of splenic lymphocytes isolated from mice were examined using fura-2 and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, respectively. Diabetes caused a significant increase in resting Ca(2+) and significantly reduced the ability of concanavalin A (Con A; a T-lymphocyte-selective mitogen) to increase Ca(2+), but not that of lipopolysaccharide (LPS; a B-lymphocyte-selective mitogen). In addition, diabetes significantly reduced Con A-stimulated but not LPS-stimulated lymphocyte proliferation. Verapamil (an L-type Ca(2+) channel blocker) inhibited Con A-induced increases in Ca(2+) and proliferation in lymphocytes from control and diabetic mice to a similar extent, respectively. These results suggest that diabetes attenuates Con A-stimulated T-lymphocyte proliferation by decreasing Ca(2+) via reduction of Ca(2+) entry through L-type Ca(2+) channels.