Oxidative Pathways of Carbohydrate Metabolism 171 



Hormonal effects on oxidative pathways in liver 



Although the activity of G6P dehydrogenase is not markedly 

 changed in the liver of diabetic rats, that of 6-PG dehydro- 

 genase falls to about half the control value. The slight depres- 

 sion in the rate of formation of COg from C-1 of glucose 

 (Table III), may be related to the low Michaelis constants of 

 these enzymes which results in the oxidation of a relatively 

 large part of the available G6P by this route. This effect is 

 reflected in the high C-l/C-6 quotient observed in liver slices 

 from diabetic rats. Treatment of the diabetic animals with 

 insulin produced a significant increase in the activity of G6P 

 dehydrogenase and 6-PG dehydrogenase (Glock, McLean and 

 Whitehead, 1956). This was accompanied by a significant rise 

 in the yield of ^^COg from [l-i*C]glucose, above both diabetic 

 and control levels. The yield of ^^COg from [6-^*0] -glucose was 

 increased even more by insulin treatment, resulting in a return 

 of the C-l/C-6 quotient towards the control value (Table III). 



Chaikoff (1953) has postulated two blocks in the metabolism 

 of glucose in the diabetic animal, one at the stage of glucose 

 phosphorylation and the other at the level of the 2-carbon 

 oxidative fragment. The above results using differentially 

 labelled glucose molecules are in accord with this. 



The results obtained with isotopes for liver slices from 

 diabetic rats do not agree with those of Bloom (1955) who 

 found a lowered value for the C-l/C-6 quotient, indicating 

 that a greater proportion of glucose was being catabolized via 

 the glycolytic route. These discrepancies may perhaps be 

 attributed to the fact that in the experiments of Bloom the 

 diabetes was more severe and of longer duration. 



In the case of liver slices from thyroxine-treated rats, the 

 isotope results indicate that the increased glucose catabolism 

 is due to a greater participation of the glycolytic pathway, 

 since the yield of ^^COg from [6-^*C]glucose only is increased, 

 and there is a significant fall in the C-l/C-6 quotient from 1 -9 

 in the control group to 1-3 in the hyperthyroid group. It 

 thus appears that despite the increased activity of enzymes of 



