PPARγ–PI3K/AKT–NO signal pathway is involved in cardiomyocyte hypertrophy induced by high glucose and insulin

Abstract

ObjectiveTo investigate the role of the PPARγ–PI3K/AKT–NO signaling pathway in cardiac hypertrophy induced by high glucose and insulin. MethodsCardiomyocyte hypertrophy induced by high glucose (25.5mmol/L) and insulin (0.1μmol/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. ResultsHGI 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 (0.1μmol/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 NG-nitro-l-arginine-methyl ester, an NOS inhibitor, partially blocked the effects of rosiglitazone (P<0.05). ConclusionThese results suggest that the PPARγ–PI3K/AKT–NO signal transduction pathway might be involved in HGI-induced cardiomyocyte hypertrophy.