Aims: Cystic fibrosis (CF) is a monogenic autosomal recessive disease caused by mutation in the cystic fibrosis gene that encodes the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). The leading complication of CF is cystic fibrosis related diabetes. The aim of this study was to investigate the presence of CFTR in pancreatic islet cells and if it influences exocytosis and secretion in pancreatic - and b- cells. Method: Patch-clamp recordings and capacitance measurements were performed on single mouse b-cells. Detection of CFTR in islet cells was investigated using confocal immunocytochemistry and insulin-and glucagon secretion was measured using RIA. Results: Human- and mouse a- and b-cells express CFTR as confirmed by immunocytochemistry. In single mouse b-cells, a membrane conductance of 0.05±0.01 nS/pF and 1.05±0.22 nS/pF (n=10) at negative and positive potentials, respectively, was activated by the cAMP-increasing agent forskolin (Sigma, USA). The conductance was significantly reduced (P<0.001) and the current almost totally inhibited in the presence of 10 mM of the CFTR-antagonist, CFTRinh-172 (Sigma, USA). Moreover, exocytosis elicited by a train of 10 membrane depolarisations and measured as an increase in membrane capacitance on single b-cells was significantly reduced by 70±10% (P<0.05, n=9) in the presence of 10 mM CFTRinh-172. Glucagon secretion meaurements on islets at 1 mM glucose indicated a similar scenario in a-cells as in b-cells. Addition of 40 mM CFTRinh- 172 reduced glucagon secretion by [asymp]22% and reduced the cAMP-amplified glucagon secretion by [asymp]23%. Conclusion: These results demonstrate that 1) CFTR is highly abundant in pancreatic islet cells on a protein level, 2) a CFTR conductance could be measured in pancreatic b-cells, 3) CFTR is involved in exocytosis and 4) CFTR potentiates glucagon secretion.