Total cellular calcium and magnesium content of cultured human peripheral blood mononuclear cells following exposure to antidiabetic drugs.
Drugs modulating the ATP-sensitive potassium (K(ATP)) channel activity are widely used for the treatment of diabetes mellitus, the target being pancreatic beta-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.
Alon
I
I
Department of Internal Medicine F, Assaf Harofeh Medical Center, Zerifin 70300, Israel.
Berman
S
S
Shteinshnaider
M
M
Efrati
S
S
Gorelik
O
O
Almoznino-Sarafian
D
D
Weissgarten
J
J
Cohen
N
N
D000328:Adult; D002118:Calcium / Q000097:blood*; D002478:Cells, Cultured; D003981:Diazoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects*; D008274:Magnesium / Q000097:blood*; D008687:Metformin / Q000494:pharmacology; D008875:Middle Aged; D015221:Potassium Channels / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D008274:Magnesium; D003981:Diazoxide; D005905:Glyburide; D002118:Calcium