Blocking p38 and JNK activation enhances islet survival and function. Effects of high glucose and IL-1β on islet integrity and viability in the presence of SB203580/SP600125 (SB/SP). A, Islet integrity was observed after 48 hours of treatment with 16.7mM glucose and 2- to 20-ng/mL IL-1β by light microscopy, and cell death was observed within 12 hours by fluorescence microscopy of Hoechst/PI double-stained islets. B, Apoptosis in islets was detected within 8 hours by immunoblot of cleaved Caspase-3. C, Effects of high glucose and IL-1β on islet function in the presence of SB203580/SP600125 (SB/SP) or TNF-α neutralizing monoclonal Ab. After exposure of islets to 16.7mM glucose and 20-ng/mL IL-1β for 24 hours, insulin release was measured by static incubation from islets pretreated with 2.8mM glucose for 60 minutes and stimulated with 16.7mM glucose for 60 minutes. Graphed results are expressed as mean ± SD determined from at least 3 independent experiments. Asterisks above bars indicate statistically significant differences (*, P < .05) in mean values for treatments compared with the stimulatory group (16.7mM glucose) based on a one-way ANOVA and Dunnett's multiple comparison post hoc test.