Glucose-stimulated insulin secretion pathway (pancreatic beta cell) (GSIS pathway)

The insulin secretion pathway in pancreatic beta cells is a tightly regulated multistep process integrating glucose, amino acids, fatty acids, hormones, and neuronal signals to control insulin release. Key steps involve glucose uptake via transporters, metabolism by glucokinase and glycolysis, rise in ATP/ADP ratio, closure of ATP-sensitive potassium channels, membrane depolarization, opening of voltage-gated calcium channels, influx of calcium, and exocytosis of insulin-containing vesicles. The process is subject to biphasic dynamics and modulation by neurotransmitters (acetylcholine, VIP, PACAP), incretin hormones, and several classes of drugs. Dysfunction or death of beta cells or the signaling pathway is central to the pathogenesis of diabetes mellitus[1][2][3][4][5][6][7][8].

Other names

Insulin secretory pathwaypancreatic beta cell insulin secretion pathwayGSIS pathwaybeta cell stimulation pathway

K_ATP channel closure (sulfonylureas, meglitinides, leading to membrane depolarization and calcium influx); GLP-1 receptor activation (increases cAMP, enhances glucose-dependent insulin secretion); Muscarinic receptor activation (increases intracellular IP3/Ca^2+^ in presence of glucose); Voltage-gated calcium channel opening (final common pathway for insulin vesicle fusion/exocytosis); Inhibition of K_ATP channels (pharmacologic stimulators)