THE METABOLISM OF THE CARBOHYDRATES 665 



the therapy of diabetes makes it advisable for us to go into the subject 

 a little more in detail here. 



Dogs are rendered diabetic by phlorhizin after a cold bath and 

 exposure in a cold room. When all of the original glycogen in the 

 body has been got rid of, as evidenced by the constancy of the G to N 

 ratio in the daily quantities of urine excreted, the substance under in- 

 vestigation is fed. If this substance contains no nitrogen and causes no 

 change in the nitrogen excretion, any increase in that of glucose must 

 obviously represent the extent to which the substance has become con- 

 verted into this sugar. On the other hand, if the substance itself con- 

 tains nitrogen, or if it causes a change in the excretion of nitrogen, it 

 becomes necessary. to calculate how much of the excreted glucose may 

 have been derived from the body protein, assuming that this can form 

 glucose, and how much from the administered substance.* 



From the results of this method it has been an easy matter to show 

 that the following substances are converted in the animal body into 

 glucose: (1) Glycol aldehyde (CH 2 OH-CHO). By placing three mol- 

 ecules of this substance together, a hexose molecule results, a synthesis 

 which can be accomplished in the chemical laboratory. The hexose formed 

 in the animal body is glucose. Glycol aldehyde may be formed in normal 

 metabolism out of glycocoll (CH 2 NH 2 COOH). 



(2) Glycerol (CH 2 OH - CHOH- CH 2 OH) may also readily be con- 

 verted into hexose in the laboratory, the possible intermediary products 

 being dioxyacetone (CH,OH - CO - CH 2 OH) and gly eerie aldehyde 

 (CH 2 OH-CHOH-CHO). Two molecules of either of these may be 

 polymerized to form a hexose molecule, and when this process occurs 

 in the animal body, the hexose formed is glucose. 



(3) Lactic acid (CH 3 CHOH - COOH) is completely converted to glu- 

 cose in the diabetic animal, and the process must involve both a re- 

 arrangement of the molecule and subsequent polymerization. " The related 

 substance, propyl alcohol (CH 3 - CH 2 - CH 2 OH) is also converted into 

 glucose in the phlorhizinized dog. As to the exact nature of the chemical 

 changes which occur as intermediary steps in the conversion of these 

 substances into glucose, we are not as yet certain, but a clue has 

 been afforded by the discovery that a substance called methylglyoxal 

 (CH 3 COCHO) can be obtained from lactic acid and also from glucose, and 

 that this substance is converted into glucose when it is administered to phlor- 

 hizinized dogs. We shall find later an important role for this substance 



"This calculation is made as follows: The amount of nitrogen in the administered substance is 

 deducted from the nitrogen excretion, and the difference, which must represent the nitrogen of the 

 body protein, is multiplied by the G to N ratio which prevailed on the day previous to that on 

 which the substance was fed. We obtain in this wav the glucose derived from the body. The 

 glucose coming from the administered substance can then be ascertained by deducting that derived 

 from the body protein from the total glucose excretion. 



