High-glucose condition reduces cardioprotective effects of insulin against mechanical stress-induced cell injury.

AIMS

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.

MAIN METHODS

Cultured neonatal rat cardiomyocytes were plated on silicone chambers, and the cells were mechanically stretched by 15% to induce cell injury.

KEY FINDINGS

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.

SIGNIFICANCE

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.