Mathematical modeling of the glucagon challenge test
Open accessAbstract
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.
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Some mathematical models exist in the literature describing postprandial endogenous glucose production suppression as a function of plasma glucose, insulin, and glucagon.
“Some mathematical models exist in the literature describing the postprandial EGP suppression as a function of plasma glucose, insulin [10, 11], and glucagon [12–15].”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [15]
The Introduction describes a mathematical model of glucose–insulin–glucagon interaction, and Methods (‘The hepatic glucose production rate’; page unavailable) models glucagon’s effect on liver glucose production. But the paper studies a glucagon challenge test, not postprandial suppression of endogenous glucose production; it also says its model neglects insulin’s effect on liver glucose production. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn these experimental conditions, this model and the other models of the literature are still suboptimal because they do not account for the glucagon evanescent effect visible in the data.
“Nonetheless, in our experimental conditions, this [11] and the other models of the literature [10, 12–15] are still suboptimal since they do not account for the glucagon evanescent effect visible in the data (Fig. 1, Panel D).”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [15]
Most existing mathematical models of postprandial endogenous glucose production suppression use plasma glucose and not endogenous glucose production as the variable to fit.
“However, most of them use plasma glucose and not EGP as a variable to fit.”
From Modeling the effect of glucagon on endogenous glucose production in healthy individuals under meal-like conditions (2025) · cites this paper as [15]
The Introduction discusses earlier glucose-homeostasis models, but does not say whether most fit plasma glucose rather than endogenous glucose production (EGP). The Methods section on the glucagon challenge test lists both blood-glucose measurements and hepatic glucose production rates; it does not establish the claimed pattern for postprandial models. Searches for postprandial EGP suppression and fitting variables found no passage addressing that comparison; page numbers were not available in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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I'm a doctor, not a mathematician! Homeostasis as a proportional-integral control systemPreprint
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- Authors
- Masroor, S., van Dongen, M. G. J., Alvarez-Jimenez, R., Burggraaf, K., Peletier, L. A., & Peletier, M. A.
- Affiliations
- Maastricht University (NL)
- Centre for Human Drug Research (NL)
- Leiden University (NL)
- Eindhoven University of Technology (NL)
- Corresponding author
- Peletier, Mark A.
- Venue
- Journal of Pharmacokinetics and Pharmacodynamics
- Published
- 2019-09-30
- Volume
- 46
- Issue
- 6
- Pages
- 553-564
- ISSN
- 1567-567X (ISSN-L)
- 1573-8744
- PMC
- PMC6868112
- OpenAlex
- W2978088004
- Cited by
- 12
- References
- 27
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Pharmacokinetics and Pharmacodynamics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- TU/e Research Portal (publishedVersion, other-oa)
- TU/e Research Portal (submittedVersion)
- TU/e Research Portal (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (639.033.008)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucose homeostasis, glucagon, insulin, G protein-coupled receptors, endocytosis, liver, hyperglycemia, mathematical model
- MeSH terms
- Blood Glucose, Glucagon, Glucose, Glucose Tolerance Test, Humans, Hyperglycemia, Insulin, Models, Theoretical, Receptors, Glucagon
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