8 J. J. R. MACLEOD
hydrogen and oxygen in the same proportion as in water (CH20).
From the combustion point of view, therefore, we may regard the
molecule as being just so much carbon. When C is burned by 02 the
volume of 02 that is used is equal to the volume of the CO2 produced;
therefore the respiratory quotient must be unity. It is different with
fat and protein. In the case of fat and protein, oxygen is required,
not only for the carbon, but for part of the hydrogen as well; there-
fore the volume of oxygen which is used will be greater than the
volume of carbon dioxide which is produced. The respiratory quotient,
therefore, is less than unity, and it is one of the achievements of
modern medical science, due to the work of Rubner, Lusk, Benedict
and others, that it is now possible to tell precisely from the respiratory
quotient what type of combustion is going on in the body at a given
time; what portion of protein and what portion of carbohydrate is
being burned. One may define diabetes as the inability of the body to
burn carbohydrate. This means that the administration of carbohydrate
to a diabetic patient will not cause the respiratory quotient to rise to
the same extent as in a normal animal. There is no alteration of the
respiratory quotient when diabetes is extreme, such as in the case in
diabetic dogs. If you feed diabetic dogs with carbohydrate, for
example, there is little or no change in the respiratory quotient. If
insulin be given with sugar to a diabetic dog, or patient, however, the
respiratory quotient rises as in a normal person. That, then, is a
fundamental observation showing that insulin makes it possible for
the sugar to be burned up. Now this is the last link in the chain of
metabolic processes through which carbohydrate passes in the animal
body, and the first link, as you all know, is the deposition of glycogen.
In diabetes, both in laboratory animals and in man, no glycogen, or
only a trace, is deposited in the liver, no matter how much sugar you
may feed to the animal. If you give insulin with sugar, however,
glycogen becomes abundant in the liver. In some experiments on
diabetic dogs, we have observed over 12% of glycogen in the livers,
and in one case, over 20%0 was found. This is the highest percentage
of glycogen that had been observed in any animal up to this time.
This shows that insulin acts on the glycogenic end of the metabolic
chain of carbohydrate as well as on its oxidative end. How these two
processes are linked together we do not know, but that the two are
affected together are obviously most significant facts.