Neuroprotective effect of GLP-1/Ex-4 against high glucose-induced toxicity, the downstream signaling pathways involved and the effect of GLP-1/Ex-4 on protecting PC12 cells from oxidative stress-induced injuries. a Exposure to 27 mg/ml glucose and GLP-1/Ex-4 (50, 100, 200, and 1,000 nM) for 96 h, cell viability was increased compared with GLP-1/Ex-4 untreated group. n = 6. b Pretreatment with GLP-1/Ex-4 protected PC12 cells from 0.025 mM H2O2-induced loss of cell viability. n = 6. c In PC12 cells, the ratio of Bax/Bcl-2 (marker of apoptosis) was elevated by high glucose (27 mg/ml) and was lowered by GLP-1/Ex-4-treatment. n = 3. d The effect of GLP-1/Ex-4 on protecting PC12 cells from high glucose (27 mg/ml) induced injury was lost in cells treated with an inhibitor of PI3K (LY294002; 50 μM) but not with an inhibitor of MAP-kinase (PD98059; 100 μM). n = 5. *P < 0.05, **P < 0.01 vs the control group; †P < 0.05 vs the high glucose or H2O2 group; #P < 0.05 vs the high glucose + GLP-1 or the high glucose + Ex-4 group