P38 plays an important role in glucolipotoxicity-induced apoptosis in INS-1 cells

Objectives. the mechanism underlying the regulation of glucolipotoxicity- induced apoptosis by mapks was examined in ins-1 cells. methods. the rat insulinoma cell line ins-1 was cotreated with glucose (30 mm) and palmitic acid (0.2 mm) (glu+pa). apoptosis was assessed by cell morphology and detection of parp cleavage. the activation of mapks was examined by western blotting using specific antibodies against the phosphorylated forms of jnk,erk1/2,and p38. results. (1) live cell imaging studies showed that treatment with glu+pa for 72 h induced significant cell death,concomitant with parp-1 cleavage and caspase-3 activation,which peaked at 96 h of treatment. (2) western blot analysis of the activation of mapks during glu+pa-induced ins-1 cell apoptosis showed that phosphorylation of p38 increased gradually and reached a peak at 96 h,which coincided with parp-1 cleavage. a transient increase of erk activation was followed by a rapid decline at 96 h,whereas jnk phosphorylation status remained unchanged in response to glu+pa. (3) phosphorylation of insulin receptor substrate (irs)-2 at 48 h of treatment triggered its degradation,which coincided with p38 activation. (4) inhibition of p38,but not jnk or erk,blocked glu+pa-induced ins-1 cell apoptosis. conclusions. p38 may be involved in the regulation of glucolipotoxicity-induced apoptosis through the phosphorylation of irs-2. © 2014 lingli zhou et al.