Total cellular calcium and magnesium content of cultured human peripheral blood mononuclear cells following exposure to antidiabetic drugs

Abstract

Drugs modulating the ATP-sensitive potassium (K_ATP) channel activity are widely used for the treatment of diabetes mellitus, the target being pancreatic β-cells. However, any cell type possessing K_ATP channels might be concomitantly affected. We investigated the metabolic effect of glibenclamide, a K_ATP channel closer, and/or diazoxide, a K_ATP channel opener, on total intracellular content of calcium (Ca) and magnesium (Mg) of cultured peripheral blood mononuclear cells (PBMC). Metformin and rosiglitazone, acting via cellular mechanisms other than K_ATP channels, were also tested. Ca and Mg were assessed in PBMC from healthy subjects following 72 h in vitro treatment with the respective drugs. Ca content increased significantly in PBMC treated with glibenclamide or rosiglitazone, however apparently via different intracellular pathways. Mg increased only following treatment with rosiglitazone. Metformin had no effect on intracellular Ca or Mg. Pretreatment with diazoxide resulted in a significant intracellular Ca and Mg loss in each experimental situation. If verified clinically, rosiglitazone-induced increase in Mg content of PBMC might prove beneficial beyond hypoglycaemic control. On the other hand, loss of intracellular Ca/Mg content following K_ATP channel opening by diazoxide might eventually result in significant intracellular Ca and/or Mg depletion.