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

Summary

The effect of BAY K 8644 on the cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) was studied in pancreatic β-cells hyperpolarized by the K⁺ channel-activating agent diazoxide. After 50–60 min preexposure to 0–20 mM glucose in the presence of 400 μM diazoxide [Ca²⁺]_i was close to the level in unstimulated β-cells. The addition of 5 μM BAY K 8644 then triggereed 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.