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Mathematical modeling of renal tubular glucose absorption after glucose load.

ABSTRACT: A partial differential Progressive Tubular Reabsorption (PTR) model, describing renal tubular glucose reabsorption and urinary glucose excretion following a glucose load perturbation, is proposed and fitted to experimental data from five subjects. For each subject the Glomerular Filtration Rate was estimated and both blood and urine glucose were sampled following an Intra-Venous glucose bolus. The PTR model was compared with a model representing the conventional Renal Threshold Hypothesis (RTH). A delay bladder compartment was introduced in both formulations. For the RTH model, the average threshold for glycosuria varied between 9.90 ± 4.50 mmol/L and 10.63 ± 3.64 mmol/L (mean ± Standard Deviation) under different hypotheses; the corresponding average maximal transport rates varied between 0.48 ± 0.45 mmol/min (86.29 ± 81.22 mg/min) and 0.50 ± 0.42 mmol/min (90.62 ± 76.15 mg/min). For the PTR Model, the average maximal transports rates varied between 0.61 ± 0.52 mmol/min (109.57 ± 93.77 mg/min) and 0.83 ± 0.95 mmol/min (150.13 ± 171.85 mg/min). The time spent by glucose inside the tubules before entering the bladder compartment varied between 1.66 ± 0.73 min and 2.45 ± 1.01 min. The PTR model proved much better than RTH at fitting observations, by correctly reproducing the delay of variations of glycosuria with respect to the driving glycemia, and by predicting non-zero urinary glucose elimination at low glycemias. This model is useful when studying both transients and steady-state glucose elimination as well as in assessing drug-related changes in renal glucose excretion.

SUBMITTER: De Gaetano A

PROVIDER: S-EPMC3906102 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Mathematical modeling of renal tubular glucose absorption after glucose load.

De Gaetano Andrea A Panunzi Simona S Eliopoulos Dimitris D Hardy Thomas T Mingrone Geltrude G

PloS one 20140129 1

A partial differential Progressive Tubular Reabsorption (PTR) model, describing renal tubular glucose reabsorption and urinary glucose excretion following a glucose load perturbation, is proposed and fitted to experimental data from five subjects. For each subject the Glomerular Filtration Rate was estimated and both blood and urine glucose were sampled following an Intra-Venous glucose bolus. The PTR model was compared with a model representing the conventional Renal Threshold Hypothesis (RTH). ...[more]

PMID: 24489817

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Project description:Iron is a trace metal, key for the development of living organisms. Its absorption process is complex and highly regulated at the transcriptional, translational and systemic levels. Recently, the internalization of the DMT1 transporter has been proposed as an additional regulatory mechanism at the intestinal level, associated to the mucosal block phenomenon. The short-term effect of iron exposure in apical uptake and initial absorption rates was studied in Caco-2 cells at different apical iron concentrations, using both an experimental approach and a mathematical modeling framework. This is the first report of short-term studies for this system. A non-linear behavior in the apical uptake dynamics was observed, which does not follow the classic saturation dynamics of traditional biochemical models. We propose a method for developing mathematical models for complex systems, based on a genetic programming algorithm. The algorithm is aimed at obtaining models with a high predictive capacity, and considers an additional parameter fitting stage and an additional Jackknife stage for estimating the generalization error. We developed a model for the iron uptake system with a higher predictive capacity than classic biochemical models. This was observed both with the apical uptake dataset used for generating the model and with an independent initial rates dataset used to test the predictive capacity of the model. The model obtained is a function of time and the initial apical iron concentration, with a linear component that captures the global tendency of the system, and a non-linear component that can be associated to the movement of DMT1 transporters. The model presented in this paper allows the detailed analysis, interpretation of experimental data, and identification of key relevant components for this complex biological process. This general method holds great potential for application to the elucidation of biological mechanisms and their key components in other complex systems.

Dataset Information

Mathematical modeling of renal tubular glucose absorption after glucose load.

Publications

Mathematical modeling of renal tubular glucose absorption after glucose load.

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