Cyclic AMP as a determinant for glucose induction of fast Ca2+ oscillations in isolated pancreatic beta-cells

The effect of glucose on the cytoplasmic Ca2+ concentration ([Ca2+]i) of pancreatic beta-cells from ob/ob-mice was examined by dual wavelength recordings of the 340/380 nm fluorescence excitation ratio of fura-2. Single beta-cells responded to 11-20 mM glucose with an initial lowering of [Ca2+]i, followed by an increase usually manifested as large amplitude oscillations (300-500 nm) with a frequency of 0.2-0.5/min (a-type). Particularly in freshly isolated beta-cells, there were also superimposed fast oscillations with frequencies of 2-8/min amplitudes in the 70-250 nM range (b-type) and sometimes pronounced [Ca2+]i transients exceeding 250 nM with durations below 10 s (c-type). After addition of 1-100 nM glucagon or 1 mM of the dibutyryl or 8-bromo derivatives of cyclic AMP, glucose generated numerous b-type oscillations superimposed on those of the a-type or on an elevated steady-state level. The duration of the b-type oscillations increased slightly when glucose was raised from 11 to 16 mM. The c-type transients probably represent a separate reaction predominantly seen when raising cyclic AMP much above its normal concentration. It is concluded that glucose can induce fast oscillations of [Ca2+]i also in isolated beta-cells, especially when measures are taken to increase their cyclic AMP content.