Glucose Metabolism and Pulsatile Insulin Release From Isolated Islets
The effects of metabolic inhibition on insulin release and the cytoplasmic Ca 2؉ concentration ([Ca 2؉ ] i ) were studied in individually perifused pancreatic islets from ob/ob mice. The modest basal secretion in the presence of 3 mmol/l glucose was pulsatile with a frequency of ϳ0.2/min, although [Ca 2؉ ] i was stable at ϳ100 nmol/l. Introduction of 11 mmol/l glucose resulted in large amplitude oscillations of [Ca 2؉ ] i and almost 20-fold stimulation of average secretion manifested as
... nifested as increased amplitude of the insulin pulses without change in frequency. Inhibition of glycolysis with iodoacetamide or mitochondrial metabolism with dinitrophenol or antimycin A reduced glucose-stimulated secretion back to basal levels with maintained pulsatility. The [Ca 2؉ ] i responses to the metabolic inhibitors were more complex, but in general there was an initial peak and eventually sustained elevation without oscillations. When introduced in the presence of 3 mmol/l glucose, the metabolic inhibitors tended to increase the amplitude of the insulin pulses, although the simultaneous elevation in [Ca 2؉ ] i occurred without oscillations. The data indicate that pulsatile secretion is regulated by factors other than [Ca 2؉ ] i under basal conditions and after metabolic inhibition. Although pulsatile secretion can be driven by oscillations in metabolism when [Ca 2؉ ] i is stable, it was not possible from the present data to determine whether insulin pulses have a glycolytic or mitochondrial origin.