Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis
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. Howev...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/8/2/30 |
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| author | Alexandre Rocca Eric Fanchon Jean-Marc Moulis |
| author_facet | Alexandre Rocca Eric Fanchon Jean-Marc Moulis |
| author_sort | Alexandre Rocca |
| collection | DOAJ |
| description | 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 <inline-formula> <math display="inline"> <semantics> <mi>β</mi> </semantics> </math> </inline-formula>-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 <inline-formula> <math display="inline"> <semantics> <mi>β</mi> </semantics> </math> </inline-formula>-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. |
| first_indexed | 2024-03-10T20:27:41Z |
| format | Article |
| id | doaj.art-031eb750c93946bf8225454a1628c7e4 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-10T20:27:41Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-031eb750c93946bf8225454a1628c7e42023-11-19T21:38:18ZengMDPI AGToxics2305-63042020-04-01823010.3390/toxics8020030Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose HomeostasisAlexandre Rocca0Eric Fanchon1Jean-Marc Moulis2LJK, Grenoble INP, CNRS, Inria, Université Grenoble Alpes, 38000 Grenoble, FranceTIMC-IMAG, UMR 5525, CNRS, Université Grenoble Alpes, 38041 Grenoble, FranceLaboratory of Fundamental and Applied Bioenergetics (LBFA), CEA, Inserm U1005, Université Grenoble Alpes, 38000 Grenoble, FranceOral 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 <inline-formula> <math display="inline"> <semantics> <mi>β</mi> </semantics> </math> </inline-formula>-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 <inline-formula> <math display="inline"> <semantics> <mi>β</mi> </semantics> </math> </inline-formula>-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.https://www.mdpi.com/2305-6304/8/2/30OGTTminimal modelcadmiumglucose response mechanism |
| spellingShingle | Alexandre Rocca Eric Fanchon Jean-Marc Moulis Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis Toxics OGTT minimal model cadmium glucose response mechanism |
| title | Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis |
| title_full | Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis |
| title_fullStr | Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis |
| title_full_unstemmed | Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis |
| title_short | Theoretical Modeling of Oral Glucose Tolerance Tests Guides the Interpretation of the Impact of Perinatal Cadmium Exposure on the Offspring’s Glucose Homeostasis |
| title_sort | theoretical modeling of oral glucose tolerance tests guides the interpretation of the impact of perinatal cadmium exposure on the offspring s glucose homeostasis |
| topic | OGTT minimal model cadmium glucose response mechanism |
| url | https://www.mdpi.com/2305-6304/8/2/30 |
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