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TRANSLATIONAL PHYSIOLOGY

The mass, but not the frequency, of insulin secretory bursts in isolated human islets is entrained by oscillatory glucose exposure

¹Larry Hillblom Islet Research Center, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, California ²Division of Endocrinology and Diabetes, School of Medicine, University of Heidelberg, Heidelberg, Germany ³Endocrine Division, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, Minnesota

Submitted 16 August 2005 ; accepted in final form 29 October 2005

Insulin is secreted in discrete insulin secretory bursts. Regulation of insulin release is accomplished almost exclusively by modulation of insulin pulse mass, whereas the insulin pulse interval remains stable at 4 min. It has been reported that in vivo insulin pulses can be entrained to a pulse interval of 10 min by infused glucose oscillations. If oscillations in glucose concentration play an important role in the regulation of pulsatile insulin secretion, abnormal or absent glucose oscillations, which have been described in type 2 diabetes, might contribute to the defective insulin secretion. Using perifused human islets exposed to oscillatory vs. constant glucose, we questioned 1) whether the interval of insulin pulses released by human islets is entrained to infused glucose oscillations and 2) whether the exposure of islets to oscillating vs. constant glucose confers an increased signal for insulin secretion. We report that oscillatory glucose exposure does not entrain insulin pulse frequency, but it amplifies the mass of insulin secretory bursts that coincide with glucose oscillations (P < 0.001). Dose-response analyses showed that the mode of glucose drive does not influence total insulin secretion (P = not significant). The apparent entrainment of pulsatile insulin to infused glucose oscillations in nondiabetic humans in vivo might reflect the amplification of underlying insulin secretory bursts that are detected as entrained pulses at the peripheral sampling site, but without changes in the underlying pacemaker activity.

pulsatile insulin secretion; oscillatory glucose; diabetes mellitus; entrainment; islet of Langerhans

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