BAY K 8644 stimulates glucose-dependent rise of cytoplasmic Ca2+ in hyperpolarized pancreatic beta-cells

The effect of BAY K 8644 on the cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in pancreatic beta-cells hyperpolarized by the K+ channel-activating agent diazoxide. After 50-60 min preexposure to 0-20 mM glucose in the presence of 400 microM diazoxide [Ca2+]i was close to the level in unstimulated beta-cells. The addition of 5 microM BAY K 8644 then triggered a rise of [Ca2+]i dependent on Ca2+ influx. The magnitude of the BAY K 8644 effect increased with the glucose concentration and was almost 10-fold higher in 20 mM than in the absence of the sugar. It is concluded that glucose can modulate Ca2+ entry through the voltage-dependent channels by a mechanism additional to depolarization. This action may help to explain why previous exposure to the sugar results in an augmented insulin response to a second challenge.