ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B-cells.

Although closure of the ATP-sensitive K+ (K+ ATP) channel produced by glucose metabolism in the B-cell has been considered mediating the major signal for glucose-induced insulin release, evidences indicating the existence of the K+ ATP channel-independent, insulinotropic action of glucose have recently been accumulated. Namely, glucose stimulates insulin release by the B-cell with a full inhibition of the K+ ATP channel closure by diazoxide, a K+ ATP channel opener, provided cytosolic calcium is elevated. Glucose clearly elicits insulin release even if the K+ ATP channel is maximally inhibited by high concentration of sulfonylurea. In this case, glucose-induced insulin release is associated with net increase, not decrease, of K+ outflow, indicating glucose is opening K+ channels. Thus, closure of the K+ ATP channel is highly unlikely to be the mechanism responsible for the insulinotropic action of glucose under these conditions. The K+ ATP channel-independent glucose action is dependent upon physiological glucose concentration (2-30 mM) and the degree of cytosolic calcium elevation. The K+ ATP channel-independent, glucose-induced insulin release shows gradually increasing monophasic pattern which temporally resembles the second phase response of glucose-induced insulin release. The role of glucose metabolism in the K+ ATP channel-independent glucose action remains to be established. Glucose action at the B-cell can now be subdivided into two classes: one is the K+ ATP channel-dependent and the other is the K+ ATP channel-independent. The two branches may be mutually interrelated to cause normal, biphasic insulin secretion.