Glucose Metabolism and Pulsatile Insulin Release From Isolated Islets

J. Westerlund, P. Bergsten
2001 Diabetes  
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
more » ... 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.
doi:10.2337/diabetes.50.8.1785 pmid:11473039 fatcat:ojrsdy44zjafppfsjqvzmrrgfy