Effects of α‐ and β‐adrenoceptor stimulation on⁴⁵Ca²⁺efflux and insulin secretion from perfused rat islets

Exposure to the β 2 ‐adrenoceptor agonist terbutaline resulted in a transient stimulation of 45 Ca 2+ efflux from 45 Ca 2+ preloaded rat islets perfused in 2 mm Ca 2+ and 8.3 mm glucose. Concomitantly, an increase in insulin secretion occurred. Under the same experimental conditions, the α‐adrenoceptor agonist noradrenaline promptly inhibited insulin release without any apparent influence on 45 Ca 2+ efflux. In contrast, in a medium containing 2 mm Ca 2+ and a low glucose concentration (2.8 mm), terbutaline stimulated insulin secretion without any apparent effects on 45 Ca 2+ efflux. Noradrenaline had no effect on insulin secretion or 45 Ca 2+ efflux in this medium. When islets were perfused with 8.3 mm glucose in a Ca 2+ deficient medium, with or without addition of the chelating agent EGTA, terbutaline induced a marginal stimulation of insulin secretion and a negligible stimulation of 45 Ca 2+ efflux. On the contrary, noradrenaline stimulated to an immediate and notable 45 Ca 2+ efflux in these Ca 2+ deficient media. Noradrenaline also clearly inhibited insulin secretion, though less markedly and with a slower onset than in islets perfused in 2 mm Ca 2+ . When the islets were perfused in a Ca 2+ deficient medium with 2.8 mm glucose, terbutaline had a slight insulin releasing effect, but stimulated 45 Ca 2+ efflux potently. Noradrenaline had no influence on insulin secretion but a weak stimulatory effect on 45 Ca 2+ efflux. The data suggest that the β 2 ‐adrenoceptor agonist terbutaline has the ability to stimulate insulin secretion in perfused rat islets, requiring extracellular Ca 2+ for the full expression of its effects. These effects may be exerted through a Ca 2+ ‐Ca 2+ exchange over the cell membrane and/or through cAMP and intracellular Ca 2+ perturbations. Moreover, terbutaline directly stimulates 45 Ca 2+ efflux, an effect inhibited by glucose. Further, the α‐adrenoceptor agonist noradrenaline can inhibit insulin secretion in the absence of extracellular Ca 2+ , but the full expression of its inhibitory action is dependent on extracellular Ca 2+ and glucose. In addition, noradrenaline stimulates 45 Ca 2+ efflux in a Ca 2+ deficient medium, an effect which appears independent of the glucose concentration.