PROGRESS OF THE ISOTOPIC METHODOLOGY lOOl 



in the organism, pyruvic acid being an intermediary of glucose formation. 

 Glucose metabolism in tissue slices from normal and from insulin- 

 injected diabetic rats, killed from 15 minutes to 48 hours after the first 

 insulin injection, was compared. Metabolism of labelled glucose involves 

 the formation of labelled glucose-6-P. As seen in Fig. 1 minute amounts 

 of labelled glucose-6-P molecules are formed only in the liver of the 

 diabetic rat prior to insulin injection. After the first injection it takes 

 10 hr until glucose-6-P is formed at a normal rate; later an accelerated 

 glucose metabolism leading to hypoglykemia is observed. 



Labelled glucose formation from labelled pyruvate is, as seen in Fig. 2, 

 markedly enhanced in the diabetic liver and it takes about 30 hours 

 after the first injection of insulin before it is depressed to its normal 



160- 



60- 



Leber glukose — glukose — 6 — P 



6 ' ' 12 



S t u n d (? n 



Fig. 1. — Effect of administration of insulin to the rat on the rate 

 of conversion of glucose-i^C into labelled glucose-6-phosphate. — 



(N: normal; D: diabetic) 



value. Later, glucose formation is brought below its normal level leading 

 to hypoglykemia, as does, as mentioned above, the abnormally increased 

 utilization of glucose. The increased glucose formation in the diabetic 

 animal was also shown in experiments in which the conversion of the 

 i^C of palmitic acid into that of glucose was made. The rate of formation 

 of labelled glucose was four times higher in the diabetic rat. 



The formation of glucose in the organism was further investigated 

 by Stetten(^) in experiments in which the labelled glucose level of the 

 organism was kept constant during the experiment by continuous 

 intravenous injection. The non-labelled glucose, formed in the organism, 

 dilutes the activity of the urinary glucose and this dilution is a measure 

 of the glucose formation. 



Denoting with R the rate of injection in mgm of glucose per hour per 

 rat, and A and a denoting the specific activities of injected and excreted 

 glucose respectively, the amount of glucose formed from non-isotopic 

 precursors, thus not through resynthesized split-products of the injected 

 labelled glucose, r = R {A/a — 1). 



