Fig. 5: Hepatic phenotype reflects glucocorticoid-induced diabetes.

Gene expression of enzymes involved in hepatic glucose metabolism (a), ketone-body synthesis (b), and lipid metabolism (c) in liver spheroids extracted at the end of co-culture. Data shown as fold change between diseased (11 mM glucose, 50 µM HCT) and healthy (5.5 mM glucose, 10 nM HCT) conditions in a box-whisker plot with median and min-max values. Symbols represent liver samples from individual co-culture replicates (circuits) from studies 1 and 2 performed at TissUse (Study 1: n = 4, Study 2: n = 4). Differences between the diseased and the healthy condition were evaluated by multiple t-tests using the Holm–Sidak method for multiple comparisons without assuming a consistent standard deviation, p values only shown for significantly different comparisons. d Glycogen storage visualized by periodic acid-Schiff (PAS) staining. Scale bar, 50 µm. e Ketone-body synthesis represented by 3-hydroxybutyrate concentration in the co-culture supernatants. Bars show mean and symbols represent co-culture replicates from three independent studies (n values summarized in Supplementary Table 1). Studies 1 and 2 were performed at TissUse and Study 3 at AstraZeneca. Differences between the diseased and the healthy condition on day 3 or day 13 were evaluated by multiple t-tests using the Holm–Sidak method for multiple comparisons without assuming a consistent standard deviation. f Intracellular lipid droplets visualized by Nile Red staining (amber color). Blue denotes DAPI-stained nuclei. Scale bar, 50 µm.