Fig. 4

A Model simulation of weight, fasting plasma glucose and insulin for a predicted continuation of the Fast-food diet for an additional 8 weeks. Prediabetic levels (28) are shown as purple dotted line. Two meals are simulated during the period, before and the predicted 12 weeks (blue and red pizza icons respectively). B Meal response simulations before (blue solid line) and after (red dashed line) the predicted 12-week Fast-food diet for plasma insulin, plasma glucose, and glucose uptake in muscle and fat tissue. C The updates made to the cell level of the model and insulin resistance (green box). The added reactions include a protein expression \(\mathrm{IRm}\), degradation of \(\mathrm{IRi}\), protein expression of \(\mathrm{GLUT}4\), and degradation of \(\mathrm{GLUT}4\mathrm{m}\). The insulin resistance influences the protein expression of \(\mathrm{IRm}\) and \(\mathrm{GLUT}4\) (green arrows). These updates enable the gradual change in total \(\mathrm{IR}\) and \(\mathrm{GLUT}4\) due to increased insulin resistance seen in D. After the 4 weeks of the Fast-food study, the total \(\mathrm{IR}\) and \(\mathrm{GLUT}4\) (solid purple) have reached the values estimated from data in Fig. 3f, g. After the additional 8 weeks, total \(\mathrm{IR}\) and \(\mathrm{GLUT}4\) (dashed purple) have gone down further towards but not completely reached the diabetic value (dotted red line, based on the diabetic values of these parameters determined in (6)). E Cell response to the simulated meals before (blue solid line) and after the 12 weeks (red dashed line), specifically the response of \(\mathrm{PKB}308-\mathrm{p}\) and \(\mathrm{IRS}1-\mathrm{p}\)