Direct measurements of increased free cytoplasmic Ca2+ in mouse pancreatic beta-cells following stimulation by hypoglycemic sulfonylureas.
The effects of the hypoglycemic sulfonylureas tolbutamide and glibenclamide on free cytoplasmic Ca2+, [Ca2+]i, were compared with that of a depolarizing concentration of K+ in dispersed and cultured pancreatic beta-cells from ob/ob mice. [Ca2+]i was measured with the fluorescent Ca2+-indicator quin2. The basal level corresponded to 150 nM and increased to 600 nM after exposure to 30.9 mM K+. The corresponding levels after stimulation with 1 microM glibenclamide and 100 microM tolbutamide were 390 and 270 nM respectively. K+ depolarization increased [Ca2+]i more rapidly than either of the sulfonylureas. It is suggested that the increased [Ca2+]i obtained after stimulation by sulfonylureas is due to depolarization of the beta-cells with subsequent entry of Ca2+ through voltage-dependent channels.
Abrahamsson
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Berggren
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Rorsman
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D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D011188:Potassium / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D000634:Aminoquinolines; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D007473:Ion Channels; D013453:Sulfonylurea Compounds; D014044:Tolbutamide; C035739:Quin2; D011188:Potassium; D005905:Glyburide; D002118:Calcium