Effects Of Curcumin On PPARγ-PI₃K/AKT-NO Activation In High Glucose And Insulin-induced Cardiomyocyte Hypertrophy

Objective: To investigate the potential effects of curcumin, one ofextractions from the root of Rhizoma Curcumae Longae, on diabeticcardiomyocyte hypertrophy induced by high glucose and insulin （HGI） andits possible influence on PPARγ-PI₃K/AKT-NO signal pathway.Methods: The cultured neonatal rat cardiomyocyte was used toobserve the effects of curcumin on cardiomyocyte hypertrophy induced byHGI （glucose at25.5mmol/L and insulin at0.1μmol/L）, and thecardiomyocyte hypertrophic responses were assayed by measuring the cellsurface area, total protein content, and atrial natriuretic factor （ANF）mRNA expression. The expressions of mRNA and protein were assayed byreal time RT-PCR and western blotting. Endothelial NO synthase （eNOS）and NO concentration in media were determined with double antibodysandwich method and nitrate reduction, respectively.Results: HGI significantly induced cardiomyocyte hypertrophy,increased the cell surface area, total protein content, and ANF mRNA expression （P<0.01）, but decreased the expressions of PPARγ, AKT andeNOS at both mRNA and protein levels, and also reduced eNOS and NOconcentration （P<0.05）, which were increased by either curcumin, in aconcentration-dependent manner （from1to10μmol/L）, or rosiglitazone（0.1μmol/L）（P<0.05）. GW9662, a selective PPARγ antagonist, couldabolish the effects of curcumin and rosiglitazone （P<0.05）. Both LY294002（a PI₃K/AKT inhibitor） and NG-nitro-L-arginine-methyl ester （a NOSinhibitor） could partially block these above effects of curcumin orrosiglitazone （P<0.05）.Conclusions: These results indicate that curcumin can inhibitcardiomyocyte hypertrophy induced by HGI, which may be mediated bypromoting the expression of PPARγ, increasing the activation ofPI₃K/AKT-eNOS signaling pathway, then elevating the release of NO.