Synchronization of mouse islets of Langerhans by glucose waveforms

Pancreatic islets secrete insulin in a pulsatile manner, and the individual islets are synchronized, producing in vivo oscillations. In this report, the ability of imposed glucose waveforms to synchronize a population of islets was investigated. A microfluidic system was used to deliver glucose waveforms to ∼20 islets while fura 2 fluorescence was imaged. All islets were entrained to a sinusoidal waveform of glucose (11 mM median, 1 mM amplitude, and a 5-min period), producing synchronized oscillations of fura 2 fluorescence. During perfusion with constant 11 mM glucose, oscillations of fura 2 fluorescence were observed in individual islets, but the average signal was nonoscillatory. Spectral analysis and a synchronization index (λ) were used to measure the period of fura 2 fluorescence oscillations and evaluate synchronization of islets, respectively. During perfusion with glucose waveforms, spectral analysis revealed a dominant frequency at 5 min, and λ, which can range from 0 (unsynchronized) to 1 (perfect synchronization), was 0.78 ± 0.15. In contrast, during perfusion with constant 11 mM glucose, the main peak in the spectral analysis corresponded to a period of 5 min but was substantially smaller than during perfusion with oscillatory glucose, and the average λ was 0.52 ± 0.09, significantly lower than during perfusion with sinusoidal glucose. These results indicated that an oscillatory glucose level synchronized the activity of a heterogeneous islet population, serving as preliminary evidence that islets could be synchronized in vivo through oscillatory glucose levels produced by a liver-pancreas feedback loop.