Figure 1. Triggering and amplifying pathways of glucose in increasing insulin secretion (GSIS) from β-cells.

Glucose enters the β-cells via the Glut2 in rodents and Glut1 in humans transporters and undergoes metabolism by the glycolytic pathway. The increase in the ATP/ADP ratio causes inhibition of the K_ATP channels. This causes the depolarization of the plasma membrane, causing the influx of Ca²⁺ through VDCC. The subsequent increase in [Ca²⁺]_c facilitates the fusion of insulin granules to the plasma membrane. This step is called the triggering pathway. The metabolism of glucose leads to generation of metabolites or second messengers that amplify the ability of [Ca²⁺]_c to increase insulin secretion. This is called the amplifying pathway of GSIS.