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KETONE BODIES
BY MICHAEL SOMOGYI
(From the Laboratory of the Jewish Hospital of St, Louis, St. Louis)
EXPERIMENTAL
TABLE I
units hrs. ng. per cent r ng. per cem per cent
M. S., male 12 0 86 1.1
3 54 0.8 -27
5 56 1.6 +45
T. E. W., male 15 0 80 0.6
1.5 65 0.6 0
6 50 1.9 +216
E. S., male 15 0 77 0.4
1.5 50 0.4 0
6 44 0.9 +I25
C. S., female 12* 0 84 0.4
1.5 60 0.3 -25
5.5 46 0.8 +1OO
A. T., “ 12* 0 81 0.4
1.5 61 0.3 -25
5.5 49 0.6 +50
___-
* 8 units of insulin were injected at the start of bhe experiment, another
4 units 1.5 hours later.
creaseand, in time, may rise well above the level shown before the
insulin injection.
The phenomenon is illustrated in Table I, which contains the re-
sults of experiments on five subjects, It may be noted that the
first phase of the processdoes not appear in an emphatic form, but
that in the second phase the ketonemic level increasesconsiderably
in every case, in one instance to the double, in another to more than
the 3-fold of the postabsorptive level.
M. Somogyi 221
hrs. li ql. per cent sg. per cent li ng. per cat WJ.per cent
I. 16 hrs. after 0 69 0.6 87 0.4
last feeding 1.5 33 0.4 32 0.3
3 51 0.3 49 0.4
5 60 0.6 32 0.7
7 31 3.1 23 2.8
10 34 4.6 37 2.6
II. Repetition of 0 74 0.9 85 0.6
Experiment 1.5 33 0.8 18 0.5
I, 3 wks. later 3 54 0.9 43 0.5
5 72 0.7 66 0.4
7 54 1.4 27 1.7
10 35 3.5 21 4.2
III. Saline substi- 0 82 0.6 88 0.4
tuted for in- 5 86 1.1 86 0.5
sulin 10 95 0.4 79 0.3
- - -
TARLE III
Increase in Ketonemia Due to Insulin Hypoglycemia in Diabetic Patient
Apr. 8-9
11 p.m. 184 0.9
1 a.m. 195 0.8
1‘
3 126 0.9
7 ‘I 88 1.0
Apr. 11-12
10 p.m. 168 0.5
1 a.m. 63 0.6
3 “ 58 1.7
7 ‘I 61 6.4
Glucose tolerance
Blood sugar, mg. per cent, after ingestion of 100 gm. glucose
0 hr.
163
ing the night. By comparing the records of the two nights, one
obtains a clear cut illustration of the causal connection between
hypoglycemia and ketosis.
Diabetic Dogs-Observations were made during protracted hypo-
glycemic states on diabetic dogs. The animals were partially
(about 90 per cent) depancreatized, and showed but slight gly-
cosuria during the first few weeks following the operation. They
were fed exclusively with horse meat (ad Zibitum) and received no
insulin injections. Glycosuria gradually increased and in about 2
TABLE IV
Changes in Ketone&a during Ins&in Hypoglycemia ,in Diabetic Dogs
Dog 4 (weighing 10.5 kilos) received 30 units of crystalline and 10 units
of protamine insulin. Dog 7 (weighing 11.5 kilos’) received 20 units of
crystalline and 10 units of pro&mine insulin.
Dog 4 Dog 7
-
Time after Time after
insulin injec- Blood sugar Blood ketone insulin in- Blood sugar Blood ketone
tion jection
hrs. mg. per cent mg. per cent hrs. mg. per cent mg. per cent
0 308 9.1 0 257 20.3
2.5 65 1.4 3 44 13.3
-
5.5 45 4.3 8.5
7.5 48 4.6 ; 38
46 15.0
9.5 31 8.7 10.5 35 24.9
- I 12 27
-I 30.4
ketonuria also set in. Still the animals maintained their initial
body weight and looked normal in every respect. In this condi-
tion they were subjected to the experiments. About 14 hours
after the last food intake, the dogs were made hypoglycemic for
extensive periods of time by the injection of both unmodified and
protamine insulin.
In Table IV are presented the blood sugar and ketone body
values obtained in two such experiments. Dog 4 was under ob-
servation for 9.5 hours after the injection of insulin, about 7.5 hours
in hypoglycemia. As may be seen, the two phases in the changes
of the ketonemic level, which could be discerned in normal subjects
and dogs, are much more conspicuous here; the blood ketones first
M. Somogyi 225
dropped from 9.1 to 1.4 mg. per cent, only to increase again to 8.7
mg. per cent as the hypoglycemic state persisted. The rather
steep rise during the last 2 hours suggests that this tendency would
have continued had the experiment not been interrupted at this
point. Extension of the period of observation to 12 hours in the
next experiment with Dog 7 proved this to be so. In this instance
ketonemia, 12 hours after the injection of insulin (about 10 hours
of continued hypoglycemia), has risen well above the level it
showed before the injection of insulin.
SUMMARY
Insulin exerts two opposite effects upon the ketonemic level: for
some time after injection it causes a decrease, but after protracted
states of hypoglycemia it effects a rise. Both of these insulin ef-
fects occur in normal as well as in diabetic men and animals, but
appear in the diabetic on a magnified scale.
1 The discovery of these fact,s grew out of perfusiou studies of liver and
other organs by Embden and his collaborators. Subsequently other
workers, employing improved analytical methods and a wide variety of
experimental approaches, concurred without exception with Embdcn’s
conclusions (9-15).
2 For a discussion and bibliography of the subject the reader is referred
to Cori’s review ((19) pp. 152-154, 201).
M. Somogyi 227
BIBLIOGRAPHY