Coordination of pancreatic islet rhythmic activity by delayed negative feedback

Insulin secretion from islets of Langerhans is rhythmic, and these rhythms are coordinated to produce oscillatory plasma insulin levels. Using a combination of microfluidics and computational modeling, we demonstrate that coordination can occur through negative feedback of the type provided by the liver, even if that feedback is delayed by several minutes. We also demonstrate that a second, slower, mode of oscillations can occur when feedback is delayed where faster oscillations are grouped into episodes.