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Mathematical modelling of stimulus-secretion coupling in the pancreatic B-cell. V. Threshold phenomenon for the response to cyclic AMP.

Recent experimental data suggest that a rise in cyclic AMP content of pancreatic islet cells may have little effect upon cytosolic Ca2+ activity. Hence, a mathematical model for stimulus-secretion coupling was designed in which cyclic AMP fails to affect Ca2+ movements in the islet cells, but augments the responsiveness to cytosolic Ca2+ of the effector system for insulin release. Provided that the latter effect of cyclic AMP becomes operative only when the nucleotide concentration exceeds a critical threshold value, the mathematical model was found suitable to predict the dynamics of both insulin release and 45Ca fluxes in islets deprived of or exposed to D-glucose, Ca2+ and a phosphodiesterase inhibitor.