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. 2020 Apr 15;8(2):30.
doi: 10.3390/toxics8020030.

Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring's Glucose Homeostasis

Alexandre Rocca  1   2 , Eric Fanchon  2 , Jean-Marc Moulis  3
Affiliations

Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring's Glucose Homeostasis

Alexandre Rocca et al. Toxics. .

Abstract

Oral glucose tolerance tests, in which the concentration of glucose is monitored in the circulation over 2 h after ingesting a bolus, probe diabetic or pre-diabetic conditions. The resulting glucose curves inform about glucose turnover, insulin production and sensitivity, and other parameters. However, extracting the relevant parameters from a single complex curve is not straightforward. We propose a simple modeling method recapitulating the most salient features of the role of insulin-secreting pancreatic β -cells and insulin sensitive tissues. This method implements four ordinary differential equations with ten parameters describing the time-dependence of glucose concentration, its removal rate, and the circulating and stored insulin concentrations. From the initial parameter set adjusted to a reference condition, fitting is done by minimizing a weighted least-square residual. In doing so, the sensitivity of β -cells to glucose was identified as the most likely impacted function at weaning for the progeny of rats that were lightly exposed to cadmium in the perigestational period. Later in life, after young rats received non-contaminated carbohydrate enriched food, differences are more subtle, but modeling agrees with long-lasting perturbation of glucose homeostasis.

Keywords: OGTT; cadmium; glucose response mechanism; minimal model.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Protocol for indirect exposure of rat litters to cadmium through their mothers.
Figure 2
Figure 2
Approximation of the plasma glucose rate of appearance in 21-day-old rats (PND21).
Figure 3
Figure 3
Modeling method to test hypotheses on the possible targets of cadmium. In the diagram, the index i spans hypotheses 1.1–3.3.
Figure 4
Figure 4
Simulations of the OGTT at PND21 for the control group, Cd1 and Cd2 groups.
Figure 5
Figure 5
Simulations of the OGTT at PND26 for the control group, Cd1 and Cd2 groups.
Figure 6
Figure 6
Simulations of the OGTT at PND60 for the control group and groups Cd1 and Cd2.
See this image and copyright information in PMC

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