Blood glucose is regulated by the release of insulin from pancreatic beta-cells via a process called exocytosis. Exocytosis is a Ca²⁺-dependent process and key players in the exocytotic process are the SNARE-proteins SNAP-25 and syntaxin 1A. Prior to exocytosis insulin granules reside in different functional pools. The readily releasable pool (RRP) consists of granules situated in the close vicinity of the voltage-dependent Ca²⁺ channels. These granules have undergone ATP-dependent priming and are ready to be released upon an increase in Ca²⁺. Granules that have not yet been primed and need to be mobilized to the release site belong to the larger reserve pool (RP). On a cellular level, first phase insulin secretion have been hypothesized to correspond to exocytosis of granules within RRP, whereas the second phase insulin secretion is associated with mobilization of granules from RP. The exocytotic process can be modulated by the second messenger cAMP. From our and others investigations it has been demonstrated that cAMP modulate exocytosis both through PKA-dependent and PKA-independent mechanism, where the latter involve the cAMP-binding protein Epac2. Using membrane capacitance measurements in combination with the patch-clamp technique, electron and confocal microscopy and subcellular fractionation techniques we have investigated the role of SNAP-25 and Syntaxin1A in the modulation of the exocytotic response. From our investigation we can demonstrate that SNAP-25 is regulating exocytosis per see, whereas Syntaxin 1A modulate exocytosis also through interaction with the Ca²⁺channels. We demonstrate that the SNARE-proteins are associated in cholesterol-rich clusters and that desorption of the clusters using a low concentration of methyl-beta-cyclodextrin (0.1 mM) results in reduced insulin secretion and a decreased exocytotic response due to migration of SNAP-25 from the plasma membrane out to the cytosol. Finally, we can demonstrate that exocytotic proteins constitute targets of small non-coding RNAS called microRNAS (miRNAS) that are up-regulated in the diabetic animal model the GK-rat. To conclude, exocytosis is a tightly regulated process in the beta-cell and a functional exocytotic machninery is significant for the beta-cell to respond satisfactory to changes in blood glucose.