Mathematical modeling of the glucagon challenge test

A model for the homeostasis of glucose through the regulating hormones glucagon and insulin is described. It contains a subsystem that models the internalization of the glucagon receptor. Internalization is a mechanism in cell signaling, through which G-protein coupled receptors are taken from the surface of the cell to the endosome. The model is used to interpret data from a glucagon challenge test in which subjects have been under treatment with a novel glucagon receptor anti-sense drug which is aimed at reducing the number of receptors in the liver. It is shown how the receptor internalization results in tolerance of the blood glucose concentration to glucagon-induced hyperglycemia. We quantify the reduction of the number of receptors using the model and the data before and after treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10928-019-09655-2) contains supplementary material, which is available to authorized users.