Figure 16.2.

Signaling pathway: Glucose, the major stimulant, via glycolysis and mitochondrial ATP energy production increases the ATP/ADP ratio that leads to the closure of the ATP-sensitive K⁺ (K_ATP) channels. The subsequent cellular depolarization activates voltage dependent calcium channels resulting in extracellular Ca²⁺ influx and fusion of insulin granules with the plasma membrane. The incretin hormone GLP-1 acts on its receptor at β cell plasma membrane to activate adenylyl cyclase and increase intracellular cAMP levels. In turn, cAMP binds and activates protein kinase A and EPAC. EPAC then functions to increase intracellular calcium level from intracellular calcium stores in the endoplasmic reticulum and to increase the number of readily releasable pool of insulin granules at the plasma membrane. The combination of these two processes results in a potentiation of insulin secretion.