Voltage-gated potassium channels as important modulators of glucose-stimulated insulin secretion in pancreatic β-cells: insights from rodent and human studies

Insulin secretion from pancreatic islet β-cells is governed by both metabolic and electrogenic pathways. The latter involves changes in membrane potential regulated by various potassium channels, including ATP-sensitive K+ (KATP) channels, Ca2+-sensitive K+ (KCa) channels, and voltage-dependent K+ (Kv) channels. Glucose metabolism elevates the ATP/ADP ratio, leading to the closure of KATP channels and subsequent membrane depolarization. Such depolarization opens voltage-dependent Ca2+ channels (vDCCs), allowing Ca2+ influx that triggers insulin release. The membrane is then repolarized through activation of KCa and Kv channels. Multiple KCa and Kv channel subtypes have been identified in insulin-secreting cells, with emerging evidence highlighting their significant modulatory roles in glucose-stimulated insulin secretion (GSIS). In this review, the current understanding and therapeutic potential of Kv channels in insulin secretion are discussed in relation to the structural features and physiological functions.