24 hr lipid infusion in 3-day high fat fed rats replicates the perturbations to fluxes seen in T1D and hyperinsulinemic-diabetic rats and implicates increased substrate supply in the excess gluconeogenesis of T1D. (a) Plasma glucose. (b) Hepatic gluconeogenesis from pyruvate (lower bars) and glycerol (upper bars). Gluconeogenesis from both pyruvate and glycerol was increased (P<0.001 and P<0.01, respectively) in lipid-infused rats. (c) TCA cycle flux from fatty acid oxidation (lower bars) and through PDH (upper bars). VTCA from fatty acid oxidation was increased and VTCA through PDH was decreased (P<0.05) in lipid-infused rats. (d), (e) Whole-body glycerol and fatty acid (palmitate) turnover. (f) Liver acetyl CoA concentration. In all panels, data are mean ± S.E. of n=6 per group. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.