Role of oscillations in membrane potential, cytoplasmic Ca2+, and metabolism for plasma insulin oscillations.

A model for the relationship between ionic and metabolic oscillations and plasma insulin oscillations is presented. It is argued that the pancreatic beta-cell in vivo displays two intrinsic frequencies that are important for the regulation of plasma insulin oscillations. The rapid oscillatory activity (2--7 oscillations [osc] per minute), which is evident in both ionic and metabolic events, causes the required elevation in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) for the exocytosis of insulin granules. This activity is important for regulation of the amplitude of plasma insulin oscillations. The frequency of the rapid oscillatory ionic activities is regulated by glucose and allows the beta-cell to respond in an analogous way, with gradual changes in [Ca(2+)](i) and insulin release in response to the alterations in glucose concentration. The slower oscillatory activity (0.2--0.4 osc/min), which is evident in the metabolism of the beta-cell, has a frequency corresponding to the frequency observed in plasma insulin oscillations. The frequency is not affected by changes in the glucose concentration. This activity is suggested to generate energy in a pulsatile fashion, which sets the frequency of the plasma insulin oscillations. It is proposed that the slow oscillations in [Ca(2+)](i) observed in vitro are a manifestation of the metabolic oscillations and do not represent an in vivo phenomenon.