[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.


CONCLUSIONS
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.
Yang
Li-yong
LY
Department of Endocrinology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China. yly_lm@sina.com
Yang
Yong-nian
YN
Chen
Zhijian James
ZJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D002994:Clofibrate / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000633:toxicity*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007340:Insulinoma / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D000077288:Troglitazone
D000924:Anticholesteremic Agents; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione; D002994:Clofibrate; D000077288:Troglitazone