Figure 6
Model describing a possible involvement of CFTR in beta-cell granular priming and exocytosis. High glucose increases intracellular ATP leading to depolarization and influx of intracellular calcium triggering exocytosis. GLP-1 and forskolin (FSK) increase intracellular cAMP, which, together with the increase in ATP, enhance the priming of insulin granules, a process that involves influx of chloride into the granules through the intragranular ClC3 channels. Our data indicate that cAMP and ATP in parallel activate CFTR. We suggest that CFTR through a still unknown mechanism regulates ANO1 and hypothesize that the influx of chloride through ANO1 supplies the intragranular ClC3 channel and thereby enhances granular priming. CFTR, Cystic Fibrosis Transmembrane conductance regulator; ANO1, Anoctamin 1 chloride channel; gSUR, granular sulfonylurea receptor; Ca2+, calcium.