Gluconeogenesis in Infancy and Childhood: I. A Method for the Study of the in vivo Gluconeogenesis from Alanine and Glycerol

Abstract

The in vivo gluconeogenesis from alanine and glycerol in infants and children was studied by an isotope method, using 14C-labeled substates with subsequent separation of the radioactive compounds by thin-layer chromatography. Seven patients, aged 2 months to 2 years 11 months, with normal carbohydrate metabolism were studied. Trace amounts of [14C]alanine were injected intravenously in four fasting patients. The 14C moved quickly from alanine to lactate, with a peak activity in lactate obtained before 5 min. From 10 min on, the label disappeared rapidly from both. An equilibrium was established between alanine and lactate, displaced towards lactate. The peak activity in glucose was reached in 10-20 min, amounting to 10% of total injected activity. In one patient, who was also studied after a meal, the disappearance rate of alanine was reduced by 50%. Despite this reduction the appearance of label in lactate was increased, whereas the amount of label in glucose was much reduced. [14C]glycerol was injected intravenously in three fasting patients. In one patient, who received only a tracer dose of glycerol, 5 times more 14C appeared in glucose than in the patients studied with [14C]alanine. In two patients receiving a glycerol load together with the [14C]glycerol, the disappearance rate of glycerol was markedly reduced, as was the conversion of carbon to glucose and lactate.

Reduced Gluconeogenesis due to Hyperinsulinism: Hormonal and Metabolic Studies in an Infant with Hypoglycemia

“…k n increased utilization rate of glucose could not account for the reduced incorporation of I4C into glucose, since the metabolic flow of label the first minutes after the single injection of a radioactive tracer is unidirectional. In the case of [14C]alanine, the appearance of label in glucose the first 5-10 min reflects mainly gluconeogenesis, whereas the later disappearance of label from glucose reflects mainly the utilization rate (14,37). In the patient described the appearance of label in glucose was greatly reduced, whereas the disappearance rate paralleled that of the control subjects (Fig.…”

“…Additionally, the highly significant inverse correlation between alanine and FFA might point to an essential role of FFA in stimulating gluconeogenesis (14,28,44). Glycerol is mainly metabolized to glucose (37). The unchanged glycerol values during glucagon treatment might therefore reflect that an increased gluconeogenesis compensated for the increased lipolysis.…”

“…The ethical aspects of isotope studies have been discussed in a previous publication (37 Plasma was obtained from heparinized venous blood immediately put into an ice bath and separated at 4'. Trasylol was added to blood intended for glucagon analysis.…”

“…The appearance of [14C] glucose was used as an index of the overall in vivo gluconeogenesis. The results in four normoglycemic patients used as control subjects and details of the method have been published previously (37).…”

Metabolic Responses to Alanine in Small-for-Gestational Age Infants: Developmental Aspects

“…Since the alanine disappearance was curvilinear in a semilogarithmic plot, in accor dance with previous studies with 14C-alanine (24), the disposal of this amino acid could not be described by a single K value. We therefore estimated a mean K value for the time period 10 -30 min after alanine infusion, assuming that the initial 10 min represented a distribu tion period (24). The mean K value thus calcu lated was considerably higher in adults than in SGA infants.…”