title: PPARγ-PI3K/AKT-NO signal pathway is involved in cardiomyocyte hypertrophy induced by high glucose and insulin.
abstract: OBJECTIVE
  To investigate the role of the PPARγ-PI3K/AKT-NO signaling pathway in cardiac hypertrophy induced by high glucose and insulin.
  
  
  METHODS
  Cardiomyocyte hypertrophy induced by high glucose (25.5 mmol/L) and insulin (0.1 μmol/L) (HGI) was characterized in rat primary cardiomyocytes by measuring the cell surface area, protein content, and atrial natriuretic factor mRNA expression level. Protein and mRNA expressions were measured by Western blotting and real time RT-PCR, respectively. A spectrophotometric assay was used to measure the enzymatic concentration of endothelial NO synthase (eNOS), and the Griess assay measured the NO concentration.
  
  
  RESULTS
  HGI induced significant cardiomyocyte hypertrophy and decreased the expression of PPARγ, AKT and eNOS at the mRNA and protein levels, which occurred in parallel with declining eNOS activity and NO concentration (P<0.05). The effects of HGI were inhibited by rosiglitazone (0.1 μmol/L), a selective PPARγ agonist (P<0.05). However, GW9662, a selective PPARγ antagonist, abolished the effects of rosiglitazone (P<0.05). LY294002, a PI3K/AKT inhibitor, and N(G)-nitro-L-arginine-methyl ester, an NOS inhibitor, partially blocked the effects of rosiglitazone (P<0.05).
  
  
  CONCLUSIONS
  These results suggest that the PPARγ-PI3K/AKT-NO signal transduction pathway might be involved in HGI-induced cardiomyocyte hypertrophy.
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Rongchun
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jiafei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Quanhua
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou 563003, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Junqing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology, Chongqing Key Laboratory of Biochemistry Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: cqjiangqs@hotmail.com.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000150:complications; D006946:Hyperinsulinism / Q000150:complications; D006984:Hypertrophy / Q000209:etiology; D007328:Insulin / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D007328:Insulin; D047495:PPAR gamma; D009569:Nitric Oxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Cardiomyocyte hypertrophy; High glucose and insulin; NO; PI(3)K/AKT; Peroxisome proliferator-activated receptor-γ