A threshold distribution hypothesis for packet storage of insulin. II. Effect of calcium.

Abstract

Phases of insulin release were studied in the perfused pancreas with glucose or calcium used as stimulators. Stimulation patterns included constant prolonged single steps, restimulations and staircase stimulations. Except at low concentrations, glucose elicited early spikes of insulin and the slowly rising second phase. In single-step experiments, total insulin in the spikes increased with higher glucose concentration. However, time patterns were the same; ratios of initial secretion rate to total insulin secreted were constant. Total insulin in the spikes was a skewed sigmoidal function of glucose concentration; mathematical differentiation of this function approximated a bell-shaped distribution curve. Staircase experiments showed that insulin released as a spike at each step did not correlate with the increment of glucose but rather with the available insulin for a given glucose concentration, minus that released in previous steps. A two-compartmental model for insulin storage has been expanded by the hypothesis that labile insulin exists as a bell-shaped distribution of packets that rapidly release insulin when their sensitivity or threshold to glucose has been reached. Glucose was maintained at permissive concentrations and calcium was perfused as continuous single steps with restimulation and as staircases. Results were qualitatively like those with glucose. Spike responses, in terms of time, were similar to each other; total insulin released as spikes depended on that insulin releasable by an absolute calcium concentration minus that released in any previous step. It was concluded that glucose and calcium act together or sequentially on the insulin packets whose threshold to stimulator varies according to a bell-shaped distribution density.