The effect of peroxisome proliferator-activated receptor alpha and gamma ligands on free fatty acid-induced INS-1 cell impairment

OBJECTIVE: To investigate the effect of peroxisome proliferator-activated receptor alpha and gamma (PPARalpha and PPARgamma) ligands on free fatty acid (FFA)-induced pancreatic beta-cell impairment. METHODS: Insulinoma cell line beta-cell (INS-1 cells) were treated with PPARalpha ligand (clofibrate) and PPARgamma ligands (troglitazone and thiazolidinedione). C, N diphenyl-N'-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) viability assay and DNA fragmentation analysis were used to evaluate the effect of PPARalpha and PPARgamma ligands on FFA-induced INS-1 cell impairment. RESULTS: The viability of INS-1 cells decreased after incubation of the cells with FFA (0.25 - 1 mmol/L) for 24 hours. FFA (1 mmol/L) was also found to induce INS-1 cell apoptosis. Comparison of the cells treated with or without clofibrate (100 micro mol/L), troglitazone (10 micro mol/L) and thiazolidinedione (100 micro mol/L), we found that these PPARalpha and PPARgamma ligands could protect INS-1 cells from the cytotoxicity of FFA, including lipoapoptosis. CONCLUSION: FFA mediates significant lipotoxicity and lipoapoptosis in beta-cells and application of PPARalpha and PPARgamma ligands might be of value in protection of beta-cells from FFA cytotoxicity.