OBJECTIVE: To explore the effect of high glucose and lipid intervention on islet cell apoptosis through the inhibition of prostate apoptosis response factor-4 (Par-4) expression and the underlying mechanisms. METHODS: The mice islet β cells (NIT-1 cells) were randomly divided into a control group, a Par-4 inhibited group, a glucose and fatty acid intervented group and a glucose and fatty acid intervented+Par-4 inhibited group. Cell apoptosis was detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), and the protein expression levels of Par-4 and glucose regulated protein 78 (GRP78) were detected by Western blot. RESULTS: Compared with the control group [(3.14 ± 1.08)%], the apoptosis rate of islet beta cell [(33.82 ± 3.15)%] in the glucose and fatty acid intervented group was significantly increased accompanied by the dramatically elevated Par-4 and GRP78 expression (both P<0.05). Compared with the glucose and fatty acid intervented group, the apoptosis rate in glucose and fatty acid intervented+Par-4 inhibit group [(18.3 4 ± 2.11)%] was significantly decreased concomitant with the significantly decreased Par-4 and GRP78 expression (both P<0.05). CONCLUSION The glucose and fatty acid-induced apoptosis of mice islet β cells could be improved through the inhibition of Par-4 expression, which might be related to reduction of endoplasmic reticulum stress.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Cell Line ; Fatty Acids ; Gene Expression Regulation ; Glucose ; Heat-Shock Proteins ; metabolism ; In Situ Nick-End Labeling ; Islets of Langerhans ; cytology ; Mice