IL-1Ra and PDTC restore glucose-stimulated insulin secretion in human islets exposed to high glucose. Islets were cultured on extracellular matrix–coated dishes for 4 days in 5.5 and 33.3 mM glucose (control) or with IL-1Ra, PDTC, and IL-1β in combination or individually. (a and c) Basal and stimulated insulin secretion during successive 1-hour incubations at 3.3 (basal) and 16.7 (stimulated) mM glucose following the 4-day culture period. (b) Insulin content. Data are represented as mean ± SEM of three experiments from three separate donors. In each experiment, the data were collected from three plates per treatment. *P < 0.01 compared with islets cultured in 5.5 mM glucose alone. **P < 0.01 compared with islets cultured in 33.3 mM glucose alone. ***P < 0.01 compared with islets cultured in 5.5 mM glucose plus IL-1β.