Figure 4

Effect of CFTR inhibition on depolarization evoked secretion and exocytosis. (A) Insulin secretion from mouse islets measured after 15 minutes incubation at 1 mM glucose (1G) in the presence of 50 mM KCl (K), 10 μM forskolin (FSK), CFTR-inh172 (CFTRinh) and GlyH-101 (GlyH) as indicated. Data are presented as mean ± SEM of n = 15 to 17, N = 4. ^†† P <0.01, ^‡ P <0.05. (B) Exocytosis in single human beta-cells measured as an increase in membrane capacitance (ΔCm; bottom left) under control conditions (Ctrl; left) and after 10 minutes pre-incubation with GlyH-101 (GlyH; right). Experiments were conducted in the presence of cAMP in the intracellular solution. (C) a summary of data in B (Ctrl; n = 6 and GlyH; n = 4). *P <0.05. Data are presented as the increases in membrane capacitance evoked by all 10 pulses of the train (∑_all), the two first pulses (∑_1–2) or the latter eight pulses (∑_3–10). (D) As in B, but the increase in membrane capacitance was measured on single mouse beta-cells and CFTRinh-172 (CFTRinh) was used as an inhibitor of CFTR. (E) Summary of data in D (Ctrl; n = 10 and CFTRinh-172; n = 7). ***P <0.001. Data are presented as in C. (F) Inward voltage-dependent current in a single human beta-cell in the presence and absence of GlyH-101 (left) and charge-voltage relationship of voltage-dependent currents (right). Data are mean ± SEM of 10 control experiments and 5 experiments in the presence of GlyH-101. (G) As in F, but experiments were conducted on mouse beta-cells (Control; n = 7 and CFTRinh-172; n = 11).