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.
Gylfe
E
E
Department of Medical Cell Biology, Uppsala University, Sweden.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese
D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D005947:Glucose; D003981:Diazoxide; D002118:Calcium