Cyclic adenosine monophosphate differently affects the response of mouse pancreatic beta-cells to various amino acids.

1. The membrane potential of mouse beta-cells was measured in parallel with 86Rb+ efflux and insulin release from mouse islets during stimulation by three types of amino acids and modulation of their effects by glucose and cyclic adenosine monophosphate (cyclic AMP) (forskolin being used to activate the adenylate cyclase). 2. In the absence of glucose, alanine and arginine accelerated 86Rb+ efflux, whereas leucine decreased it. They all depolarized the beta-cell membrane and slightly increased insulin release. Forskolin had little effect on 86Rb+ efflux, consistently potentiated insulin release but induced electrical activity only in the presence of leucine. 3. The effects of the three amino acids on 86Rb+ efflux and beta-cell membrane potential were not qualitatively altered by a non-stimulatory concentration of glucose (3 mM). However, the release of insulin induced by leucine alone or with forskolin was markedly amplified, in contrast to that of alanine or arginine, which was inhibited. 4. In the presence of a threshold concentration of glucose (7 mM), the three amino acids accelerated 86Rb+ efflux and depolarized the beta-cell membrane. With alanine and arginine, spike activity was transiently observed and coincided with a short-lived increase in insulin release. With leucine, slow waves with superimposed bursts of spikes occurred and were accompanied by a sustained release of insulin. Forskolin alone also triggered slow waves and bursts of spikes, and increased insulin release. Both effects were larger in the presence of arginine, but not in the presence of alanine. Forskolin considerably increased the electrical and secretory effects of leucine. 5. A higher concentration of glucose (10 mM) induced slow waves with bursts of spikes in all cells and stimulated insulin release. Alanine, arginine and leucine increased 86Rb+ efflux, electrical activity and insulin release. However, the changes produced by the three amino acids displayed different time course, amplitude and characteristics. Forskolin potentiated insulin release and electrical activity induced by glucose alone. These effects were not augmented by alanine, but markedly amplified by arginine or leucine. 6. Several conclusions can be drawn from this study. The three types of amino acids depolarize the beta-cell membrane by different mechanisms and produce distinct patterns of electrical activity. Slow waves with bursts of spikes occur only if a decrease in K+ permeability contributes to the depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)