Pancreatic beta-cell glucose–insulin regulatory axis (GSIS axis)

The pancreatic beta-cell glucose–insulin regulatory axis is a complex physiological system that couples blood glucose levels to the secretion of insulin to maintain metabolic homeostasis (StatPearls, 2023). This axis involves a sequence of events starting with glucose uptake via transporters, followed by glucose metabolism and ATP production, which leads to the closure of ATP-sensitive potassium (K-ATP) channels (Rorsman & Ashcroft, 2018). The resulting membrane depolarization opens voltage-gated calcium channels, triggering the influx of calcium ions that promotes the exocytosis of insulin-containing granules (PubMed, 28439034). Dysregulation of this axis is a hallmark of diabetes mellitus, where impaired glucose sensing or insulin secretion leads to chronic hyperglycemia. Pharmacological interventions often target specific components within this axis, such as K-ATP channels or incretin receptors, to restore or enhance insulin secretion in response to elevated glucose levels (NIDDK, 2022). Because this axis represents a broad biological pathway rather than a single molecular target, it is typically categorized as a biological system or signaling network in drug discovery contexts.

Other names

Glucose-stimulated insulin secretion (GSIS) pathwayBeta-cell stimulus-secretion couplingPancreatic glucose-sensing axisInsulin secretory pathway

Modulation of insulin secretion through K-ATP channel closure, voltage-gated calcium channel activation, and incretin receptor signaling.