Periodicity of insulin secretion comprises multiple cycles with different duration in perfused rat islets

Insulin secretion from pancreatic islets has been found to be periodic by in vivo and in vitro experiments. The pacemaker which regulates the periodicity may be localized in the central nervous system or in the pancreas, though the precise location and the mechanisms of generating pacing have not been determined. In order to solve these problems, we examined the period of secretory cycles of insulin in isolated islets using a prolonged perfusion system, and investigated the effects of glucose and other agents on these periods. Isolated islets from male Wistar rats were enclosed in a millipore holder and were perfused with MEM containing 1 mg/ml glucose at a flow rate of 0.3 ml/min for 240 min. The effluent was collected at 1-min intervals to measure insulin secretion. The results were analyzed by the maximum entropy method to demonstrate the periodicity of insulin secretion. When islets were perfused with 1 mg/ml glucose, the periodicity comprised five cycles with different duration: 71.5 +/- 14.6 min, 29.8 +/- 3.4 min, 19.2 +/- 1.5 min, 11.6 +/- 2.1 min and 4.3 +/- 0.4 min. This indicates the presence of a pacemaker within the islets, although, in vivo, participation of a higher center to control periodicity has to be taken into account. Further, the presence of a long cycle (71.5 +/- 14.6 min) of insulin secretion which previously has only been observed in vivo was first demonstrated in this in vitro study. The cycles were consistent even in islets which were desensitized to glucose by cultivating in a high glucose medium for 5 days before perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)