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.