The effect of gliquidone on KATP channels in pancreatic β-cells, cardiomyocytes, and vascular smooth muscle cells.

摘要: Abstract Aims Sulfonylurea drugs exert an insulinotropic effect through ATP-sensitive potassium (K ATP ) channel inhibition in pancreatic islet cells. These channels are also expressed cardiomyocytes and vascular smooth muscle cells (VSMCs), suggesting potential for adverse cardiovascular effects. We evaluated the effects of Gliquidone (Glq) on sulfonylurea receptors HIT-T15 (SUR1), (SUR2A), VSMCs (SUR2B). Methods The concentration-dependent Glq (0.001–500 μM) K were assessed using whole-cell patch clamp cells, rat cardiomyocytes, VSMCs. Parallel studies Glibenclamide (Glb) (0.001–10 μM) Gliclazide (Glc) (0.01–500 μM)were conducted as controls. Results In HIT–T15 Glb exhibited lowest IC 50 (0.03 μM), compared to (0.45 μM) Glc (1.21 μM). However, had higher cardiomyoctes VSMCs, (119.1 vs. 0.01 149.7 vs . 0.09 μM, respectively), that is more selective β-cells than Glb. Thus, may have fewer side Conclusions a highly SUR secretagogue with moderate affinity β-cells, but low Our data reveal non-selective nature Glb, evidenced by high binding all three cell types examined.