Insulin is secreted in discrete insulin secretory bursts. Regulation of insulin release is accomplished almost exclusively by modulation of insulin pulse mass, while the insulin pulse interval remains stable at ~4 minutes. It has been reported that in vivo insulin pulses can be entrained to a pulse interval of ~10 minutes 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 versus constant glucose we questioned (1) whether the interval of insulin pulses released human islets is entrained to infused glucose oscillations and (2) whether exposure of islets to oscillating versus constant glucose confers an increased signal for insulin secretion. We report that oscillatory glucose exposure does not entrain insulin pulse frequency but 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=n.s.). The apparent entrainment of pulsatile insulin to infused glucose oscillations in non-diabetic humans in vivo may reflect amplification of underlying insulin secretory bursts that are detected as entrained pulses at the peripheral sampling site, but without changes in underlying pacemaker activity.