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+ (KATP) channel, most likely triggers the first phase. The second phase is produced by gradual augmentation and potentiation of Ca2+-triggered insulin release by the KATP channel–independent, nonionic signals. Protein acylation may be involved in the nonionic signaling. In patients lacking functional KATP 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 KATP channel–independent, most likely nonionic, glucose action alone is sufficient for the first-phase response.