Effect of CFTR inhibition on insulin secretion measured in isolated human and mouse pancreatic islets. (A) Insulin secretion from human islets at different glucose in the absence or presence of forskolin (FSK) and GlyH-101 (GlyH) as indicated (n = 42 to 45, N = 11). (B) Insulin secretion from human islets at 1 mM glucose (1G) or 16.7 mM glucose (16.7G) in the absence and presence of GLP-1 and GlyH-101 as indicated (n = 17 to 19, N = 5). (C-D) Insulin secretion from mouse islets at 1 mM glucose (1G) or 16.7 mM glucose (16.7G) in the absence or presence of FSK, GLP-1, CFTRinh-172 (CFTRinh) and GlyH-101 (GlyH) as indicated (n = 12 to 21, N = 4 to 9). (E) Insulin secretion from mouse islets at 1 mM glucose (1G) in the absence or presence of FSK and inhibitors as indicated (n = 9–12, N = 4). (F) Insulin secretion from mouse (left) and human (right) islets in the absence of FSK to demonstrate the lack of effect of the inhibitors (mouse: n = 10, N = 5; human n = 12, N = 3). (G) Localization of CFTR (yellow) and insulin (red) in fixed single islet cells (left) from human (top) and mouse (bottom), detected using confocal immunocytochemistry. Scale bar 5 μm. Images are representative of 37 beta-cells from three human donors and 23 beta-cells from three mice. Ratio of the fraction of CFTR (right) in the plasma membrane region (P1) as compared to the cytosolic region (P2) for human (top) and mouse (bottom) beta-cells. Data are presented as mean ± SEM. ***P <0.001 16.7 G vs 1 G, ††P <0.01 FSK or GLP-1 vs respective G alone, †††P <0.001 FSK vs respective G alone and ‡P <0.05 CFTRinh or GlyH vs 16.7 G and FSK alone, ‡‡‡P <0.001 GlyH vs 16.7G and FSK alone.
Edlund et al. BMC Medicine 2014 12:87 doi:10.1186/1741-7015-12-87