Two major pathways are implicated in the stimulation of insulin secretion by glucose. The K1-ATP channel-dependent pathway in- volves closure of these channels, depolarization of the b-cell mem- brane, acceleration of Ca21 influx, and a rise in cytosolic free Ca21 ((Ca21)i). The K 1 -ATP channel-independent pathway potentiates the stimulation of exocytosis by high (Ca21)i. To determine whether this second pathway is influenced by the configuration of the channel, we compared the effects of glucose on (Ca21)i and insulin secretion in