A multiscale modelling approach to assess the impact of metabolic zonation and microperfusion on the hepatic carbohydrate metabolism
Fig 2
Metabolic features of the periportal (PPH), pericentral (PCH) and mean (MH) hepatocyte (A) Simulated glucose exchange fluxes of the PPH (red), MH (green) and PCH (blue). Positive values of the glucose exchange flux correspond to net glucose uptake, negative values correspond to net glucose release. External glucose was varied between 3 and 12 mM. Experimental data were taken from [24, 26–28]. (B) Reported (black) concentration ranges of selected metabolites and simulated concentration values for the PPH (red), MH (green) and PCH (blue). Note that the experimental concentration values were obtained in liver homogenates or cultures of isolated hepatocytes and thus represent average values across different types of hepatocytes. Data were taken from various experimental sources [29–37]. (C) Average ratio of measured protein abundances in hepatocytes stemming preferentially from the periportal and pericentral region. Vertical lines indicate standard deviations. The circles indicate abundance ratios used to calibrate the model for the PPH and PCH. Experimental data are from various sources [6–21]. (D) Simulated glycogen concentration in PPH (red), MH (green) and PCH (blue) during a starvation-refeeding experiment. The initial state at t = 0 was obtained by simulating as 24h fasting period with a plasma glucose level of 4 mM. At t = 0 the plasma glucose level was elevated to 10 mM for 24 hours and then again reduced to 4 mM. Experimental data were taken from [25].