Glucose-induced [Ca²⁺]_i oscillations in voltage-clamped δ-cells. Glucose induces spontaneous Epac2-dependent but PKA-independent [Ca²⁺]_i spikes in voltage-clamped δ-cells. (A) Left: Holding current (I; middle) and changes in [Ca²⁺]_i (ΔF/F₀; bottom) measured in parallel from an SST-GCaMP3 δ-cell voltage-clamped at −70 mV in the presence of 1 mM or 20 mM glucose as indicated (top). Right: Bar graph of the AUCs of [Ca²⁺]_i at 1 and 20 mM glucose as indicated. Data are presented as mean values ± SEM for six independent experiments with totals of 6 and 34 events at 1 mM and 20 mM glucose, respectively. *, P < 0.05 vs. 1 mM glucose. (B–D) as in A, but experiments were conducted in islets pretreated with 10 µM thapsigargin (B; three independent experiments with 2 and 17 events at 1 mM and 20 mM glucose, respectively), 25 µM ESI-05 (C; three independent experiments with 8 and 17 events at 1 mM and 20 mM glucose, respectively), or 1 µM myr-PKI (D, four independent experiments with 5 and 20 events at 1 mM and 20 mM glucose, respectively). All experiments were conducted using perforated patch whole-cell technique.