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

Aims: Sulfonylurea drugs exert an insulinotropic effect through ATP-sensitive potassium (K-ATP) channel inhibition in pancreatic islet cells. These channels are also expressed in cardiomyocytes and vascular smooth muscle cells (VSMCs), suggesting potential for adverse cardiovascular effects. We evaluated the effects of Gliquidone (Glq) on sulfonylurea receptors in HIT-T15 cells (SUR1), cardiomyocytes (SUR2A), and VSMCs (SUR2B). Methods: The concentration-dependent effects of Glq (0.001-500 mu M) on K-ATP channels were assessed using whole-cell patch clamp in HIT-T15 cells, rat cardiomyocytes, and VSMCs. Parallel studies using Glibenclamide (Glb) (0.001-10 mu M) and Gliclazide (Glc) (0.01-500 mu M) were conducted as controls. Results: In HIT-T15 cells, Glb exhibited the lowest IC50 (0.03 mu M), as compared to Glq (0.45 mu M) and Glc (1.21 mu M). However, Glq had higher IC50 in cardiomyoctes and VSMCs, as compared to Glb (119.1 vs. 0.01 and 149.7 vs. 0.09 mu M, respectively), suggesting that Glq is more selective to beta-cells than Glb. Thus, Glq may have fewer side effects in cardiomyoctes and VSMCs. Conclusions: Glq is a highly selective SUR secretagogue with moderate affinity to b-cells, but low affinity to cardiomyocytes and VSMCs. Our data also reveal the non-selective nature of Glb, as evidenced by high binding affinity to K-ATP channels in all the three cell types examined. (C) 2015 Elsevier Ireland Ltd. All rights reserved.