Mathematical modeling of the glucagon challenge test

Saeed Masroor,Marloes G J Van Dongen,Mark A Peletier,Koos Burggraaf,Ricardo Alvarez-Jimenez,Lambertus A Peletier

doi:10.1007/s10928-019-09655-2

Abstract

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.

Highlights

Insulin and glucagon are two major hormones in the regulatory system of blood glucose
Schneck et al [8] presented a mechanistic model for glucose–insulin–glucagon interaction and used it for studying an oral glucokinase activator. Their model is mostly concerned with modeling the glucagon secretion process whereas the purpose of this study is to model the effect of glucagon on hepatic glucose production (HGP)
We started by describing the interaction between glucose and two associated regulatory hormones: insulin and glucagon

Summary

Introduction

Insulin and glucagon are two major hormones in the regulatory system of blood glucose. Insulin is secreted by the pancreas, especially when the concentration of blood glucose is high. It promotes the uptake of glucose from the blood into tissues. Glucagon is a hormone that has an impact on glucose–insulin homeostasis through its receptor. It is secreted by the pancreas when levels of blood glucose are low and facilitates the release of glucose from its glycogen storage in the liver into the bloodstream.

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