136 Claude A. Villee 



glucose utilization is, therefore, — 5 micromoles per g. per 

 hour. At term, the true glucose utilization is —7-5 micro- 

 moles per g. per hour, glucose production is zero, and the net 

 glucose utilization is also —7-5 micromoles per g. per hour. 

 Hence, although the average net utilization of glucose is 

 fairly constant from 15 weeks to term, this is in fact due to 

 concomitant decreases in both the production and utilization 

 of glucose. 



The production of glucose by the liver has been shown to be 

 mediated by the enzyme glucose-6-phosphatase (de Duve, 

 Berthet, Hers and Dupret, 1949; Swanson, 1950), a reaction 

 in which glucose-6-phosphate is converted to glucose plus 

 inorganic phosphate. The glucose-6-phosphate is derived 

 from glycogen via phosphorylase and glucose-1 -phosphate, or 

 by gluconeogenesis from other carbon compounds by a reversal 

 of glycolysis. The human foetal liver gains the ability to 

 secrete glucose only after 12 to 16 weeks of development 

 (Villee, 1953a). Before that time it is unable to regulate the 

 concentration of glucose in the foetal blood stream. 



The placenta does have the ability to secrete glucose early 

 in pregnancy but loses this ability as gestation proceeds. 

 The placenta thus could regulate the concentration of glucose 

 in foetal blood early in development but not later. 



The ability of a tissue incubated in vitro to secrete glucose 

 into the incubation medium may be tested in three ways. 

 First, if glucose production exceeds glucose utilization, direct 

 chemical analysis of the medium will reveal the net increase 

 in the amount of glucose present. Second, whether or not 

 there is a net increase in glucose concentration, glucose 

 production can be detected by using 14 C -labelled glucose in 

 the incubation medium and measuring the specific activities 

 of glucose isolated from the medium before and after incuba- 

 tion. If the tissue produces glucose, the unlabelled glucose 

 molecules produced will dilute the labelled molecules of glucose 

 present in the medium and the specific activity will therefore 

 decrease as incubation proceeds. Third, the tissue may be 

 incubated in the presence of 14 C -labelled pyruvate, or in the 



