Figure 2.

Effects of IR activation on insulin secretion. Insulin autocrine stimulation of β-cells can induce positive or negative feedback on insulin release. Positive feedback (right, green arrowheads): activation of the IR/IRS-1 pathway induces Akt phosphorylation, which increases intracellular Ca²⁺ release from the ER and SNARE protein levels and leads to increased insulin release from β-cells. Negative feedback (left, red arrowheads): insulin stimulation activates the IR/IRS/PI3K pathway, resulting in hyperpolarization of membrane K_ATP channel and a reduction in Ca²⁺-stimulated insulin release.