Direct measurements of increased free cytoplasmic Ca2+ in mouse pancreatic β‐cells following stimulation by hypoglycemie sulfonylureas

Abstract

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 dispered and cultured pancreatic β-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 μM glibenclamide and 100 μM 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 β-cells with subsequent entry of Ca²⁺ through voltage-dependent channels.