Synchronization of Mouse Islets of Langerhans by Glucose Waveforms

Xinyu Zhang, Arij Daou, Tuan M. Truong, Richard Bertram, Michael G. Roper

Pancreatic islets secrete insulin in a pulsatile manner, and the individual isle ts 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 approximately 20 islets while imaging Fura-2 fluorescence. 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 wi th constant 11 mM glucose, oscillations of Fura-2 fluorescence were observed in individual islets, but the average signal was non-oscillatory. Spectral analysi s and a synchronization index (lambda) 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 lambda, which can range from 0 (unsynchronized) to 1 (perfect synchronization), was 0.79 + 0.10. 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 lambda 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 lo op.