Abstract
In livers of normal fed rats, 12-h and 96-h starved rats, fat-fed rats, and alloxandiabetic ketotic rats, the concentrations of lactate, pyruvate, ATP, ADP, NAD +, fructose 1,6-diphosphate, triosephosphate, glycogen, and total nitrogen, were determined under conditions in vivo by the freezing-stop technique. Lactate and pyruvate concentrations were also determined in livers from rats which received intraportal infusions of sodium caproate. The liver concentrations of β-hydroxybutyrate, acetoacetate, malate and oxaloacetate were estimated in livers from the 12-h starved and the fat-fed groups. Studies in vitro were carried out with isolated perfused livers of normal and severely diabetic rats for the determination of lactate, pyruvate and total ketone-body concentrations in the medium, and the concentrations of lactate, pyruvate, ATP and ADP in the perfused liver tissue. The perfusion experiments were carried out with or without intraportal infusions of sodium caproate. The results reveal no correlation between the extent of fatty acid oxidation as shown by ketone-body formation and the redox state of the three NAD +-NADH systems in equilibrium with the substrate pairs: lactate-pyruvate, malate-oxaloacetate and β-hydroxybutyrate-acetoacetate. Thus, the increased reduction of the cytoplasmic NAD +-NADH system in livers of severely diabetic rats is not the consequence of enhanced fatty acid oxidation during diabetes. Sodium caproate leads to a significant increase in the uptake of lactate and pyruvate by isolated, perfused livers. While the ATP-ADP ratio was lower in diabetic livers, the ATP concentration showed no decrease. The total concentration of ATP and ADP, as well as the concentration of NAD +, was significantly higher in diabetic livers. The stationary concentrations of fructose 1,6-diphosphate and triosephosphate showed no increase in livers of fat-fed, starved or diabetic rats. No evidence for the existence of a block in glycolysis at the triosephosphate dehydrogenase (EC 1.2.1.12) step could be found, under these conditions.
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