INSULIN 9
With regard to fat metabolism, it is well known that in diabetes the
process goes seriously wrong. In the first place, the transportation
of fat is affected so that the blood and the liver become loaded with
this substance. The resulting lipemia is a serious symptom in diabetes,
but it quickly disappears on the administration of insulin. In the
second place, the combustion of fat which is at the other end of the
metabolic chain is seriously deranged in diabetes. In a normal animal
the combustion of fat proceeds by stages. The long fatty acid chain
is broken off bit by bit by oxidation at the so-called beta C. atom,
and the end products of this combustion are water and carbon dioxide.
There is a stage in the breaking down process, however, at which it
is apt to hesitate, that is, at the stage of butyric acid (CH3CH2CH2
COOH) which, it will be seen, contains four carbon atoms. In dia-
betes butyric acid, instead of becoming completely oxidized, becomes so
only as far as beta-oxy-butyric acid (CH3CHOH CH2COOH) and
the closely related acetocetic acid and acetone, which are responsible
for the symptoms of coma. It is said that this hesitation in the final
oxidation of fatty acid is due to the fact that there is no carbohydrate
combustion going on. Fat burns in the fire of carbohydrates, and
since in the diabetic no carbohydrate is being burned, fat combustion
also becomes incomplete. It smokes as it were, and the smoke accumu-
lates in the body in the foirm of beta oxybutyric acid. Since insuiin
affects the combustion of carbohydrates, it should also affect this
ultimate combustion of fat, and such has been found to be the case.
Insulin stirs up the carbohydrate fires so that fat combustion proceeds
to its completion, and the so-called acetone bodies disappear from
the urine.
Finally, let me allude briefly to some work which we are engaged
in pertaining to the mechanism of the action of insulin, but which is
as yet incomplete. When rabbits are injected with varying quantities
of insulin, it is remarkable how, during the first half hour after injec-
tion, the blood sugar always comes down at nearly the same rate.
This would seem to indicate that the process by which the blood sugar
becomes lowered must be an intravascular one. It looks as if it must
be something occurring in the blood itself. There are two reactions
that might occur in blood itself: One is glycolysis, and the other is a
union of sugar with something else, or its polymerization into glycogen.
If blood be removed from the body and insulin added to it, the rate
of glycolysis is not altered. Neither is the rate of glycolysis different