Importance of Nonionic Signals for Glucose-Induced Biphasic Insulin Secretion

Abstract

Glucose induces biphasic insulin secretion by the islet β-cell. Based on recent knowledge on glucose signaling in the β-cell, the underlying mechanisms for this biphasicity could be envisaged as follows. Glucose-induced elevation of cytosolic free Ca²⁺ concentration, which is due to the electrophysiological events that originate in closure of the ATP-sensitive K⁺ (K_ATP) channel, most likely triggers the first phase. The second phase is produced by gradual augmentation and potentiation of Ca²⁺-triggered insulin release by the K_ATP channel–independent, nonionic signals. Protein acylation may be involved in the nonionic signaling. In patients lacking functional K_ATP channels, however, the first phase of glucose-induced insulin secretion is clearly retained, casting doubt on the simplistic view outlined above. In this pathological condition, the K_ATP channel–independent, most likely nonionic, glucose action alone is sufficient for the first-phase response.