Stimulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) activity by low concentrations of circulating glucose in perfused rat liver

Abstract

(Received I1 Febrmary 1975) 1. After nicotinic acid treatment, rat liver glycogen is depleted and phosphoenolpyruvate carboxykinase activity increased, to about twice the initial value. 2. The increase in phosphoenolpyruvate carboxykinase activity promoted by nicotinic acid is prevented by cycloheximide or actinomycin D, suggest-ing that this effect is produced by synthesis of the enzyme de novo. 3. Despite the enhancement of phosphoenolpyruvate carboxykinase activity and glycogen depletion, which occurs 5h after the injection of nicotinic acid, the gluconeogenic capacity of liver is low and considerably less than the values found in rats starved for 48h. 4. When the livers of well-fed rats are perfused in the presence of low concentrations of glucose, the activity of phosphoenotpyruvate carboxykinase significantly incteases compared with the control. 5. This increase is not related to the glycogen content, but seemns to be also the result of synthesis of the enzyme de novo, since this effect is coumteracted by previous treatment with cycloheximide or actinomycin D. 6. Phosphoenolpyruvate carboxykinase activity is not increased in the presence of low concentrations of circulating glucose when 40mnM-imidaiole (an activator of phosphodiesterase) is added to the perfusion medium. 7. Addition of dibutyryl cyclic AMP to the perfusion medium reguftsg in an incrtease in phosphoenolpyruvate carboxykinase activity, in spite of the presenCe of normal concentrations of circulating glucose. On the other hand, the concentration of cyclic AMP in the liver increases when that of glucose in the medium is low. 8.These results suggest that, in the absence of hormonal factors, the regulation of phosphoenolpyruvate carboxykinase can be accomplished by glucose itself, inadequate concentrations of it resulting in the induction of the enzyme. The mediator in this regulation, as in hormonal regulation, seems to be cyclic AMP.

Prematurity in the Rat

“…groups, 1 or 2 h after delivery. These values are about half of those observed in well-fed adult rat liver (17). Liver fructose 1,6-diphosphatase activity remained unchanged in both groups throughout the observation period but signifi cant differences were found between groups, the activities being lower in preterm rats.…”

True

“…Systemic effects of raised blood glucose induced by nicotinamide and carbogen do not appear to have been considered in the literature with respect to tumour radiosensitization, although attempts to increase tumour pO 2 by decreasing the consumption of oxygen, and hence radioresponse, have been (Biaglow et al, 1998). It has been known for many years that metabolism of nicotinamide results in glycogen breakdown and a consequent increase in blood glucose (Ammon and Estler, 1967;Moreno et al, 1985). However, we have not found any previous reports (other than our own work, Stubbs et al, 1998) of carbogen-induced hyperglycaemia and the mechanism of this effect must be speculative.…”

Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog.

“…Whether the cause of the decreased appearance of [14C]alanine in [14C]-glucose is direct inhibition of gluconeogenesis or stimulation of glycolysis it must reflect a decrease in the net flux of gluconeogenic carbon to glucose within the liver. Evidence is available from in vitro experiments to support the contention that glucose per se can inhibit gluconeogenesis (31)(32)(33).…”