INTRACELLULAR CALCIUM AND HYDROGEN-IONS IN DIABETES-MELLITUS

Diabetes mellitus is a multi-component syndrome that is often complica ted by angiopathy which is partly due to enhanced platelet functions. Using fluorescent dyes 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and Fura-2 AM, changes was evaluated in the concentration of baseline and thrombin-stimulated increases in intracellular ionized ca lcium (Ca-i(2+)) relative to hydrogen ions in the platelets from contr ol, insulin-treated, and non-treated diabetic rats. The cytosol of pla telets from the diabetic rats were more acidic compared to the insulin -treated and normal control rats, The increased intracellular hydrogen ion concentration [H+] or decreased pH (pH) in the diabetic rat plate lets is associated with an increased baseline [Ca2+](i). Upon stimulat ion with thrombin, the mean peak [Ca2+](i) for the insulin-treated (30 9 +/- 97 nmol/L) and untreated (339 +/- 135 nmol/L) diabetic rats was significantly higher than the concentration for the normal rats (213 /- 101 nmol/L). Treatment with insulin attempts to correct the diabete s-induced elevation in the baseline of [Ca2+](i) and intracellular H+. These results suggest that the relationships between Ca2+ and H+ rela tive to binding sites are similar in the intra- and extracellular comp artments. It is our conclusion that the enhanced platelet activity and associated development of vascular diseases in diabetes may be due to an increased intracellular H+ that caused an increased baseline [Ca2](i) in diabetes mellitus.