Figure 1.

VIP activates the VPAC2 signaling pathway in pancreatic islets. VIP binding to VPAC2 receptors on β-cells activates AC and increases the concentration of cAMP, which activates PKA and the Epac family. PKA triggers the closure of ATP-dependent K⁺ channels, resulting in plasma membrane depolarization, and the opening of voltage-gated Ca²⁺ channels, which leads to an increased influx of Ca²⁺. Activation of Epac mobilizes the release of Ca²⁺ from internal storage. Both the processes cause elevated intracellular Ca²⁺ levels and the release of insulin through exocytosis.