Quinine and the Stimulus-Secretion Coupling in Pancreatic β-Cells: Glucose-Like Effects on Potassium Permeability and Insulin Release*

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Abstract
Quinine increases insulin release in vitro. The objective of the present study was to define both its mode of action and the role of the potassium (K) permeability of the β- cell membrane in the stimulus-secretion coupling. Quinine (25– 50 μM) doubled basal insulin release and markedly potentiated glucose-induced secretion in isolated rat islets. Its effects were most marked (10-fold) at threshold concentrations of glucose (5.6 mM) and required the presence of extracellular calcium. The augmentation of insulin release by quinine was not affected by atropine, propranolol, or the Na antagonist tetrodotoxin, but was markedly increased by theophylline or dibutyryl cAMP. Quinine also potentiated the insulinotropic action of glyceraldehyde, leucine, and arginine. Quinine decreased the efflux of 86Rb+ in perifused islets in the presence or absence of glucose; it also inhibited the influx, but did not affect the net uptake of 86Rb+. 45Ca2+ influx and net uptake at various glucose concentrations were increased by quinine, which also increased 45Ca2+ efflux from perifused islets whenever extracellular calcium was present. In a calcium-free medium, quinine slightly decreased 45Ca2+ efflux in the absence of glucose, but not in its presence. 2- Deoxyglucose impaired glucose metabolism by islet cells, increased their K permeability (86Rb+ efflux), decreased 45Ca2+ uptake, and inhibited insulin release. Quinine did not prevent the inhibition of glucose metabolism by 2-deoxyglucose, but restored a lower K permeability in islet cells, a normal 45Ca2+ uptake, and a normal insulin release. These results strongly suggest that quinine stimulates and potentiates insulin release by mimicking the effect of glucose to decrease the K permeability of the β-cell membrane, leading to Ca2+ influx through voltagedependent channels.