title: The effect of gliquidone on KATP channels in pancreatic β-cells, cardiomyocytes, and vascular smooth muscle cells.
abstract: OBJECTIVE
  Sulfonylurea drugs exert an insulinotropic effect through ATP-sensitive potassium (KATP) 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 μM) on KATP channels were assessed using whole-cell patch clamp in HIT-T15 cells, rat cardiomyocytes, and VSMCs. Parallel studies using Glibenclamide (Glb) (0.001-10 μM) and Gliclazide (Glc) (0.01-500 μM)were conducted as controls.
  
  
  RESULTS
  In HIT-T15 cells, Glb exhibited the lowest IC50 (0.03 μM), as compared to Glq (0.45μM) and Glc (1.21μM). However, Glq had higher IC50 in cardiomyoctes and VSMCs, as compared to Glb (119.1 vs. 0.01 and 149.7 vs. 0.09 μM, respectively), suggesting that Glq is more selective to β-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 β-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 KATP channels in all the three cell types examined.
authors.affiliation: Division of Endocrinology and Metabolism Internal Medicine, West China Hospital, Sichuan University, Chengdu, China; Division of Endocrinology & Metabolism, The First People's Hospital of Chengdu, Chengdu, China.
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Division of Endocrinology and Metabolism Internal Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Hao-Min
authors.initials: HM
authors.lastname: Tian
authors.affiliation: Laboratory of Anesthesia and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Liao
authors.affiliation: Laboratory of Anesthesia and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Division of Endocrinology and Metabolism Internal Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Gou
authors.affiliation: Division of Endocrinology and Metabolism Internal Medicine, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Xie
authors.affiliation: Division of Endocrinology and Metabolism Internal Medicine, West China Hospital, Sichuan University, Chengdu, China. Electronic address: liusysc@163.com.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D064233:Sulfonylurea Receptors
chemical_list: D054086:KATP Channels; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; C010969:gliquidone
keywords: ATP-sensitive potassium channel; Cardiomyocyte; Gliquidone; HIT-T15 cell; Patch clamp technique; Vascular smooth muscle cell