title: High-glucose condition reduces cardioprotective effects of insulin against mechanical stress-induced cell injury.
abstract: OBJECTIVE
  Mechanical stress induces cardiomyocyte injury and contributes to the progression of heart failure in patients with hypertension. In this study, we investigated whether insulin exerts cardioprotective effects against mechanical stretching-induced cell injury, and whether the protective effect is influenced by high-glucose condition.
  
  
  METHODS
  Cultured neonatal rat cardiomyocytes were plated on silicone chambers, and the cells were mechanically stretched by 15% to induce cell injury.
  
  
  RESULTS
  Mechanical stretching increased reactive oxygen species (ROS) and decreased mitochondrial inner membrane potential (DeltaPsi(m)), eventually leading to cell death by apoptosis and necrosis. Insulin activated the phosphoinositide 3 (PI3) kinase/Akt pathway and reduced apoptosis and necrosis by suppressing ROS increase and preserving DeltaPsi(m). However, high-glucose condition attenuated the insulin-induced Akt phosphorylation and cardioprotection. To investigate the mechanisms that attenuated the effects of insulin in high-glucose condition, we examined the expression of tensin homologue deleted on chromosome 10 (PTEN), which is a negative regulator of the PI3 kinase/Akt pathway. The expressions of PTEN and phosphorylated PTEN were significantly decreased by insulin, and those effects were attenuated in high-glucose condition.
  
  
  CONCLUSIONS
  The present results suggest that insulin prevents mechanical stress-induced cell injury which otherwise lead to heart failure. Furthermore, we found that high-glucose condition prevented the decrease in PTEN expression and the cardioprotective effects induced by insulin.
authors.affiliation: Department of Laboratory Examination and Diagnostics, Faculty of Medicine, Oita University, Yufu-city, Oita, Japan. teshima@med.oita-u.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Teshima
authors.forename: Naohiko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Luong Cong
authors.initials: LC
authors.lastname: Thuc
authors.forename: Satoru
authors.initials: S
authors.lastname: Nishio
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nagano-Torigoe
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Kaori
authors.initials: K
authors.lastname: Ezaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Yufu
authors.forename: Masahide
authors.initials: M
authors.lastname: Hara
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Saikawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009336:Necrosis / Q000188:drug therapy; D051059:PTEN Phosphohydrolase / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D002316:Cardiotonic Agents; D007328:Insulin; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D005947:Glucose