title: Damage to vascular endothelial cells by high insulin levels is associated with increased expression of ChemR23, and attenuated by PPAR-gamma agonist, rosiglitazone.
abstract: OBJECTIVE
  This study investigated the effect of different insulin concentrations on the activity of vascular endothelial cells (VECs), and the role of PPARγ activator rosiglitazone (RGZ) on the expression of the chemerin receptor, ChemR23, in insulin-treated human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  Cell viability was determined in HUVECs treated with different insulin concentrations. Immunofluorescence staining was used to detect ChemR23 expression in insulin-treated HUVECs. Western blot assays were used to evaluate ChemR23 and PPARγ protein expression in insulin-treated HUVECs after pretreatment with PPARγ activator (RGZ) or inhibitor (GW9662).
  
  
  RESULTS
  High insulin concentrations significantly inhibited HUVEC cell viability compared to low insulin concentrations, and this inhibition was attenuated by pretreatment with RGZ. High concentrations of insulin caused a significant upregulation of ChemR23 and a significant downregulation of PPARγ. These effects were attenuated by RGZ pretreatment, while PPARγ antagonist, GW9662 reversed this attenuation.
  
  
  CONCLUSIONS
  ChemR23 upregulation may play a role in VEC damage caused by high concentrations of insulin. The protective effect of PPARγ activation in VECs may be mediated via ChemR23 downregulation.
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Fei
authors: F
authors: Hao
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Jia-Wei
authors: JW
authors: Mu
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Hui-Juan
authors: HJ
authors: Zhang
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Hong-Yu
authors: HY
authors: Kuang
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Qiu-Xia
authors: QX
authors: Yu
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Meng-Meng
authors: MM
authors: Bai
authors: Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, China.
authors: Ping
authors: P
authors: Meng
mesh_terms: D000813:Anilides / Q000494:pharmacology; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C102741:CMKLR1 protein, human; D007004:Hypoglycemic Agents; D007328:Insulin; D047495:PPAR gamma; D019707:Receptors, Chemokine; D045162:Thiazolidinediones; D000077154:Rosiglitazone