KIC- and glucose-stimulated ISR by islets cultured in RPMI 1640 medium containing either 11 mm (A) or 3 mm (B) glucose for 40 h. Islets were perifused in the presence of 3 mm glucose for 90 min. Subsequently, 10 mm KIC was added and removed, and 20 mm glucose and nimodipine were added to and removed from the inflow at the times shown on the graph. Fractions were collected and insulin was assayed to determine the ISR (average ± S.E., n = 4). Statistical analysis was carried out by comparing steady-state values (determined by averaging data obtained in the final 15 min of each experimental condition) before and after each change in medium composition using a paired t test (*, p < 0.05; **, p < 0.01).