PULSATILE INSULIN RELEASE FROM MOUSE ISLETS OCCURS IN THE ABSENCE OF STIMULATED ENTRY OF CA2+

Pancreatic islets are known to respond to a raise of the glucose conce ntration with Ca2+-induced 2-3-min pulses of insulin release. The repo rts of cyclic variations of circulating insulin in the fasting state m ade it important to explore whether insulin release is also pulsatile in the absence of stimulated entry of Ca2+, Individual pancreatic isle ts were isolated from a local colony of ob/ob mice and perifused under conditions allowing dual wavelength recordings of the cytoplasmic Ca2 + concentration ([Ca2+](i)) with fura-2 and measurements of insulin wi th ELISA technique. At 3 mM of glucose, [Ca2+](i) remained at a stable low level, but insulin was released in pulses with a frequency of 0.4 1 +/- 0.02 min(-1), determined by Fourier transformation of original a nd autocorrelated data, Pulses of basal insulin release were also seen when glucose was omitted and 1 mu M clonidine or 400 mu M diazoxide w as added to a glucose-free medium, The results indicate that pulsatile insulin release can be generated in the absence of stimulated entry o f Ca2+, A tentative explanation for this phenomenon is inherent fluctu ations in the ATP production of the beta cells.