Changes in Energy Metabolite and Regulatory Hormone Concentrations and Net Fluxes across Splanchnic and Peripheral Tissues in Fed and Progressively Fasted Ewes

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Abstract
Effects of fasting on glucose, ketone bodies, free fatty acids (FFA), insulin and glucagon metabolism were studied in eight fed, five 1-d-fasted and five 3-d-fasted ewes. The 3-d fast decreased blood glucose from 55 to 49 mg/dl due to a 40% reduction in its splanchnic output. Plasma FFA increased from 280 to 872 and 912 µM in 1- and 3-d-fasted ewes concomitant with increased omental and peripheral release. Hepatic uptake of FFA increased three- and fourfold and was concentration-dependent. Consequently, hepatic release of acetoacetate and β-hydroxybutyrate increased from -43 and 276 to 90 and 1304 µmol/min, respectively, in 3-d-fasted ewes. Alimentary ketogenesis ceased entirely due to lack of substrate and gut tissue was actually utilizing both ketone bodies by d 3 of fast. Lower hindquarter utilization of both ketone bodies increased with increasing circulating concentrations. Insulin seemed to be the major mechanism of regulation of glucose, FFA and ketone body metabolism since pancreatic production and arterial concentrations of insulin decreased with progressive fasting. No changes were observed in glucagon concentrations or net fluxes, and therefore the role of glucagon was passive and secondary to that of insulin.