Regulation of calcium fluxes in rat pancreatic islets. Quinine mimics the dual effect of glucose on calcium movements.

The effects of quinine and 9-aminoacridine, two blockers of potassium conductance in islet cells, on 45Ca efflux and insulin release from perifused islets were investigated in order to elucidate the mechanisms by which glucose initially reduces 45Ca efflux and later stimulates calcium inflow in islet cells. In the absence of glucose, 100 microM quinine stimulated 45Ca net uptake, 45Ca outflow rate and insulin release. Quinine also dramatically enhanced the cationic and the secretory response to intermediate concentrations of glucose, but had little effect on 45Ca net uptake, 45Ca fractional outflow rate and insulin release at a high glucose concentration (16.7 mM). The ability of quinine to stimulate 45Ca efflux depended on the presence of extracellular calcium, suggesting that it reflects a stimulation of calcium entry in the islet cells. In the absence of extracellular calcium, quinine provoked a sustained decrease in 45Ca efflux. Such an inhibitory effect was not additive to that of glucose, and was reduced at low extracellular Na+ concentration. At a low concentration (5 microM), quinine, although reducing 86Rb efflux from the islets to the same extent as a non-insulinotropic glucose concentration (4.4 mM), failed to inhibit 45Ca efflux. In the presence of extracellular calcium, 9-aminoacridine produced an important but transient increase in 45Ca outflow rate and insulin release from islets perifused in the absence of glucose. In the absence of extracellular calcium, 9-aminoacridine, however, failed to reduced 45Ca efflux from perifused islets. It is concluded that quinine, by reducing K+ conductance, reproduces the effect of glucose to activate voltage-sensitive calcium channels and to stimulate the entry of calcium into the B-cell. However, the glucose-induced inhibition of calcium outflow rate, which may also participate in the intracellular accumulation of calcium, does not appear to be mediated by changes in K+ conductance.