Figure 1.

Cyclic AMP signaling in insulin secretion. Schematic drawing of a β-cell and the involvement of cAMP in insulin secretion stimulated by glucose and amplified by hormones. Glucose metabolism generates ATP, which inhibits ATP-sensitive K⁺ channels and causes voltage-dependent Ca²⁺ influx. Elevation of [Ca²⁺]_i triggers exocytotic release of insulin granules. ATP also promotes formation of cAMP, which amplifies secretion via Epac2 and protein kinase A (PKA). Activation of G_s-coupled receptors by e.g. glucagon, GLP-1, or GIP leads to cAMP formation and enhancement of insulin release. Cyclic variations in metabolism, [Ca²⁺]_i and cAMP concentration caused by incompletely understood feedback circuits result in pulsatile insulin secretion.