Figure 1.

Schematic representation of glucose stimulated insulin secretion (GSIS) and subcellular Ca²⁺ dynamics in pancreatic β-cells. Ca²⁺ transporters within a pancreatic β-cell responsible for balancing Ca²⁺ homeostasis are the following: in the plasma membrane: PMCA: plasma membrane Ca²⁺-ATPase, NCX: Na⁺/Ca²⁺ exchanger; within the endoplasmic reticulum: SERCA: sarco/endoplasmic reticulum Ca²⁺-ATPase, RyR: ryanodine receptor, IP₃R: inositol 1,4,5-trisphsphate receptor, VDAC: voltage dependent anion-selective channel; within mitochondria: NCLX: mitochondrial Na⁺/Ca²⁺ exchanger, PTP: permeability transition pore, MCUC: mitochondrial Ca²⁺ uniporter complex. Red arrows depict the process of glucose-stimulated insulin secretion. After uptake of glucose via GLUT2/1 mitochondrial ATP production is boosted leading to a closing of plasma membrane located ATP-sensitive K⁺ channels (K_ATP). The resulting shift in membrane potential activates PM voltage-dependent Ca²⁺ channels (VDCC) stimulating Ca²⁺-induced Ca²⁺ release which ultimately leads to exocytosis of insulin-containing granules.