FIGURE 3.

Secretagogue-induced insulin secretion from INS-1 insulinoma cells and pancreatic islets increases with iPLA₂β expression level and is suppressed by pharmacologic inhibition of p38 MAPK. In A, pancreatic islets isolated from wild-type mice (WT; blue or yellow bars) or from transgenic mice (TG; red or green bars) that overexpress iPLA₂β in islet β-cells were preincubated (1 h, 37 °C) with the p38 MAPK inhibitor (85) PD169316 (20 μm) (yellow or green bars) or vehicle (blue or red bars) and then placed in fresh KRB medium containing 0 or 20 mm d-glucose without or with 2.5 μm forskolin and incubated (30 min, 37 °C). In B, similar experiments were performed with INS-1 insulinoma cells stably transfected with empty vector (V; blue or yellow bars) or with a construct that causes overexpression of iPLA₂β (OE; red or green bars) that were incubated without (blue or red bars) or with (yellow or green bars) PD169316 and with 0 or 20 mm d-glucose and 0 or 2.5 μm forskolin, as in A. At the end of the incubation period, aliquots of medium were removed for measurement of insulin content as described under “Experimental Procedures.” Mean values are displayed, and S.E. values (error bars) are indicated (n = 3). *, p < 0.05 for the comparison of the indicated condition and the analogous condition in which incubation was performed in the presence of PD169316.