Fig. 5.

Exendin-4 attenuates ER stress via SIRT1. a HepG2 cells were pretreated with 50 nM exendin fragment 9-39 [Ex (9-39)], a GLP-1receptor antagonist, for 6 h and were then treated with exendin-4, a GLP-1 receptor agonist, for 24 h. The expression of GLP-1R and SIRT1 protein was measured by Western blot. b HepG2 cells were exposed to PA (400 μM) and treated with or without Ex-4 (100 nM) for 24 h. Nicotinamide (NAM) was added to the cells treated with both PA and Ex-4. Inositol-requiring 1α (IRE1α), activating transcription factor 6 (ATF6), pancreatic ER kinase (PERK), X-box binding protein 1 (XBP1), ER degradation-enhancing alpha-mannosidase-like 1 (EDEM1), glucose-regulated protein 78 kDa (GRP78/BiP), C/EBP homologous protein (CHOP), and growth arrest and DNA damage (GADD34) were measured by quantitative real-time RT-PCR and normalized based on the β-actin control. Data are expressed as the mean ± SEM. *p < 0.05, **p < 0.01 compared with the control, ⁺ p < 0.05, ⁺⁺ p < 0.01 compared with PA, and ^# p < 0.05, ^## p < 0.01 compared with PA + Ex-4. c Cells were transfected with 10 nM siRNA against SIRT1 for 24 h and were then exposed to PA (400 μM) and treated with or without Ex-4 (100 nM) for 24 h. The expression of P-PERK, P-IRE1α, ATF6, XBP1, and CHOP protein was measured by Western blot