Time and amplitude regulation of pulsatile insulin secretion by triggering and amplifying pathways in mouse islets

Glucose-induced insulin secretion is pulsatile. We investigated how the triggering pathway (rise in β-cell Ca²⁺]_i) and amplifying pathway (greater Ca²⁺ efficacy on exocytosis) influence this pulsatility. Repetitive Ca²⁺]_i pulses were imposed by high K⁺+ diazoxide in single mouse islets. Insulin secretion (measured simultaneously) tightly followed Ca²⁺]_i changes. Lengthening Ca²⁺]_i pulses increased the duration but not the amplitude of insulin pulses. Increasing glucose (5–20 mmol/l) augmented the amplitude of insulin pulses without changing that of Ca²⁺]_i pulses. Larger Ca²⁺]_i pulses augmented the amplitude of insulin pulses at high, but not low glucose. In conclusion, the amplification pathway ensures amplitude modulation of insulin pulses whose time modulation is achieved by the triggering pathway.