Metabolic fluxes relative to net glucose uptake reveal flux rerouting through NADPH-producing reactions.A, flux map highlighting the absolute metabolic changes associated with G6pc2 KO in βTC3 cells. Fluxes highlighted in red are upregulated compared to G6pc2 WT βTC3 cells. B, subset of selected metabolic fluxes normalized to net glucose uptake (VGK Net) in G6pc2 WT and KO βTC3 cells at 5 mM (left) and 11 mM (right) glucose concentrations estimated using MFA. Data represent means ± SEM, ∗p < 0.05 (n = 3). C, flux map highlighting the metabolic changes relative to VGK Net associated with G6pc2 KO in βTC3 cells. Fluxes highlighted in red are upregulated compared with G6pc2 WT βTC3 cells. D, cytoplasmic calcium levels at 5 and 11 mM glucose concentration measured in G6pc2 WT and KO βTC3 cells. Results are the mean 245 measurements from WT cells and 256 measurements from KO cells taken at 5-s intervals for a total of 300 s. ∗∗∗p < 0.01 (n = 3). KO, knockout.