Figure 1.

Insulin biosynthesis and secretion by pancreatic β-cells. Insulin biosynthesis begins with transcription of the insulin gene in the nucleus and translation of the mRNA into pre-proinsulin. Upon translocation into the ER, the signaling peptide is removed, thereby creating proinsulin. Proinsulin is folded and stabilized by a disulfide bond in the ER and then transported into the secretory granules, where proinsulin is cleaved to C-peptide and insulin. Glucose is the major stimulus of insulin secretion. Glucose is transported across the β-cell plasma membrane via the glucose transporter [GLUT2 (rodent) or GLUT1 (human)]. Then, glucose is metabolized to pyruvate via glycolysis and further metabolized and produces ATP in the mitochondria through oxidative phosphorylation. An increase in the ATP/ADP ratio leads to closure of the ATP-sensitive K⁺ channels and membrane depolarization, which results in the opening of L-type voltage-gated Ca²⁺ channels (L-VGCCs). The influx of extracellular calcium ions into the β cells induces the exocytosis of secretory vesicles with insulin.