Schematic diagrams showing the roles of SNAP23 in pancreatic β cells. (A) SNAP25 forms a complex with syntaxin1A and VAMP2, which allows insulin granules to effectively dock and fuse at the plasma membrane. (B) The SNAP23–syntaxin1A–VAMP2 complex has a weaker ability to fuse insulin granules at the plasma membrane. Thus, the existence of SNAP23 will obstruct the insulin secretion by SNAP25. (C) MF286 blocks SNAP23 to form a complex with syntaxin1A and VAMP2. (D) In wild-type cells (top), both SNAP23 and SNAP25 are expressed and localized at the plasma membrane. SNAP23 and SNAP25 compete with each other for binding to syntaxin1A and VAMP2. Because the SNAP25–syntaxin1A–VAMP2 complex is more efficient in exocytosis, SNAP23 acts as a competitive inhibitor of insulin secretion. In contrast, depletion (middle) or inhibition (bottom) of SNAP23 results in an increase in the SNAP25–syntaxin1A–VAMP2 complex. Therefore, secretion of insulin is increased. For simplification, syntaxin1A and VAMP2 are not presented in this scheme.