Fig 1.
Graphical representation of the whole-body glucose metabolism as considered in our model, according to the notation introduced in [62].
Only the organs/tissues for which a variable has been explicitly included in the model are depicted in the figure (other key organs/tissues of glucose metabolism, like pancreas and brain, are not displayed in the figure even if their effect has been indirectly taken into account in model equations, see Results and S1 File for details). Adipose tissue is colored in yellow to highlight that it is the part for which a model at the cellular level is also provided (see Fig 2). Green ovals (hormones) and orange rectangles represent model variables; arrows represent mass transfer (white head), stimulation (black head) and inhibition (T head).
Fig 2.
Graphical representation of the model describing the insulin signaling in adipocytes at the cellular level, according to the notation introduced in [62].
Solid arrows represent state modification, while dashed arrows indicate reaction stimulation. Protein complexes are colored in yellow, green ovals represent the active and inactive feedback protein, while the orange rectangles represent all the other components of the cellular model. The plasma membrane of the adipose cell is represented in yellow and it separates the cytosol (light yellow horizontal lines) from the interstitial fluid (blue and white vertical lines). The variables I and G indicate insulin and glucose concentration in plasma (compartment not represented), which regulate the amount of interstitial insulin (INSA) and glucose (GtA), respectively. For the sake of simplicity, we highlighted the five variables linking the cellular level to the whole body description (namely plasma insulin, interstitial insulin, plasma glucose, interstitial glucose and intra-adipocitary glucose) by adding the corresponding names in parenthesis.
Fig 3.
Model dynamics at the whole body level.
Each plot represents one variable dynamics. The normal glucose regulation (NGR) and T2DM conditions are shown in green and black, respectively. The red and blue lines delimit the physiological lower and upper ranges of variables (see also Table B in S1 File).
Fig 4.
Model dynamics of the insulin signaling in adipocytes at the cellular level (only a subset of key variables is represented).
The normal glucose regulation (NGR) and T2DM conditions are shown in green and black, respectively.
Fig 5.
Model simulation and data fitting, normal glucose regulation (NGR) condition.
Each plot represents the corresponding time courses for the indicated insulin signaling intermediaries. The experimental data are taken from Nyman et al. [26] and are represented with circles and error bars (a.u. indicates arbitrary units). The time course represents the model simulation.
Fig 6.
Model simulation and data fitting, T2DM condition.
Each plot represents the corresponding time courses for the indicated insulin signaling intermediaries. The experimental data are taken from Nyman et al. [26] and are represented with circles and error bars (a.u. indicates arbitrary units). The time course represents the model simulation.