For normal glucose homeostasis, insulin release by the pancreatic beta cell
is vital. Until recently, it was thought that glucose-induced ionic events
, such as closure of the ATP-sensitive K+ (K-ATP) channels, membrane depola
rization, activation of the L-type voltage-dependent Ca2+ channels, Ca2+ in
flux and elevation of cytosolic free Ca2+, constitute the main signalling p
athway in beta-cell stimulus-secretion coupling. However, since the disc ev
ery of 'non-ionic' glucose actions in the beta cell by the Aizawa and Henqu
in laboratories in 1991, data have accumulated th at strongly indicate the
physiological relevance of this signalling pathway. In this review, Torn Ai
zawa and colleagues discuss how the K-ATP channel-Ca2+ hypothesis was formu
lated, what was overlooked in the hypothesis, and then provide a comprehens
ive view of stimulus-secretion coupling in the beta cell, with an emphasis
on non-ionic glucose actions.