THE DI ASTATI C ACTI VI TY OF THE BLOOD I N EXPERI -

MENTAL HYPERGLYCEMI A.
BY HOWARD T. KARSNER, M.D., HERBERT L. KOECKERT, M.D.,
SPENCER A. WAHL, M.D.
(From tke Department of Pathology of tke Sckool of Medicine, Western Reserve
University, Cleveland.)
(Received for publication, May 7, 1921.)
I.
INTRODUCTION.
Since the demonstration of diastatic activity of the blood and lymph by
Magendie, Bial, grid RShman, the production of hyperglycemia and glycosuria
by Claude Bernard, and the demonstration of the influence of the pancreas upon
carbohydrate metabolism by yon Meting and Minkowski, numerous investiga-
tors have conducted further studies. I t has long been known that the injection
of such substances as adrenalin, strychnine, morphine, and more recently, saliva,
pitnitrin, and various other glandular extracts possessing amylolytic properties
leads in some instances to the development of hyperglycemia and glycosuria.
In spite of considerable conflict concerning the diastatic content of the blood in
these conditions the mass of evidence so far accumulated supports the belief
that little or no change is produced. However, Watanabe found in rabbits that
the intravenous injection of human saliva and the intraperitoneal administration
of sodium bicarbonate (5 or 10 gin.) each produced an increase, while the paren-
teral administration of soluble starch and the intravenous injection of sodium
bicarbonate (5 or 10 gm.) each produced a slight increase in the diastatic activity
of the blood.
Further observations have been made concerning the r61e of the pancreas.
Following ligation of the duct of Wirsung, Schlesinger reported an increase in
the diastatic activity of the blood; Clerc and Loeper verified this result in rabbits;
Gould and Carlson, working with dogs, ligated both pancreatic ducts and found
a marked increase in the diastatic power of the serum, which they assumed to
be due to absorbed amylopsin; King observed an increased diastatic activity in
the serum and urine upon ligation of both pancreatic ducts. Wohlgemuth,
Noguchi, and King reported a quantitative increase in the diastatic activity of
the urine following ligation of both pancreatic ducts.
349
350 EXPEI~ rM-~.NTAL H Y P E RG L Y CE M IA
Bainbridge and Beddard, as well as Carlson and Luckhardt, reported that in
cats the concentration of blood diastase is not materially changed by excision
of the pancreas; Schlesinger states that pancreatectomy leads to complete disap-
pearance of amylase from the blood. Otten and Galloway found that in dogs
immediately following pancreatectomy the concentration of blood diastase
sinks rapidly, then rises slightly, remaining at a constant level for a time but
never retur.ning to the normal level again. King reports a reduction in the amount
of blood diastase in depancreatized dogs. Mflne and Peters obtained a decided
increase in the blood diastase after complete pancreatectomy.
Recently, the question of the diastatic activity of the blood has been more
accurately studied in human diabetes. Myers and KiUian (1917)reportedan
increase in the diastatic activity of the blood in cases of human diabetes. Still
more recently (November, 1920), Lewis and Mason, employing essentially the
same method as Myers and KiUian, found a distinct decrease in the blood diastase
in human diabetes.
IL
Method.
The met hods for the determination of the diastatic activ-
i t y of the blood have varied from time to time but all depend upon
a hydrolytic process. Wohlgemuth (1908) based his method upon
the hydrolysis of starch into erythrodextrin by amylase, using the
simple iodine reaction. Myers and K_illian (1917) devised a met hod
based upon the hydrolysis of starch into glucose, using Myers and
Bailey' s modification of the Lewis-Benedict method for the blood
sugar determination.
In our laboratory the met hod used was essentially the same as
t hat described by Myers and Killian with the exception of the substi-
tution of Folin and Wu' s method for blood sugar determination.
Our experiments consisted (1) in observing the effect upon blood
diastase in rabbits after the subcutaneous injection of phlothizin,
uranyl nitrate, morphine sulfate, and adrenalin; (2) in noting the
effect of puncture of the floor of the fourth ventricle; and (3) in
observing the effect upon the content of blood diastase in completely
depancreatized dogs. The controls consisted in noting (1) the
effect of diet; (2) the effect produced by repeated bleeding of the
animal comparable to the procedure followed in the experiment;
(3) the effect of asphyxia; (4) the effect of ether anesthesia; and (5)
the effect of a surgical operation similar in extent to pancreateetomy. 1
I All operations were performed under ether anesthesia.
H. T. KARSNER, H. L. KOECKERT, AND S. A. WAHL 351
The rabbits were fed upon a diet consisting of carrots, oats, and
water; t he di et for t he dogs was composed of a balanced mi xt ure of
beef heart, casein, crackers, salt, lard, and water. The specimens
of blood were t aken from t he ear veins of t he rabbits and by cardiac
punct ure from t he dogs. All blood diastase det ermi nat i ons were
st art ed within 10 mi nut es after withdrawal of t he blood. Th.e.exami-
nations in t he case of t he rabbits were made 2 hours following t he
injection and t he punct ure; and t hen at intervals of 24 hours unt i l
t he blood sugar had ret urned to normal or t he ani mal died. After
pancreat ect omy in dogs t he exam{nations were made i mmedi at el y
following t he operation in two cases; in all animals 2 hours later,
and t hen at 12 hour intervals until t he animal succumbed.
All drugs were given subcutaneously in t he following doses: mor-
phine sulfate, 2 cc. of a 4 per cent solution (80 mg. ); adrenalin, chlo-
ride, 2 cc. of 1: 1, 000 solution; uranyl nitrate, 3 rag.; pMorhizin,
0.25 gin. The Eckhard operation wa s performed in two of t he suc-
cessful punct ure experiments. The pancreatectomies consisted in
complete removal of t he pancreas by usual operative technique under
ether anesthesia wi t hout morphine.
III.
EXPERIMENTS.
Three rabbits were given phlorhizin subcutaneously in doses of
0.25 gm. dissolved in warm distilled wa t e r . I n one ani mal wi t h
a normal diastatic act i vi t y ranging between 3 and 8 mg. per 100 cc.
t he first injection of pMorhizin produced no change in diastatic
activity, but a second injection 5 days later was followed in 24 hours
by a figure for diastase of 20 mg. At this time, however, t hat ani mal
had been bled t en times in 28 days and t he result was probabl y in
par t influenced by t he repeated bleedings, and therefore can only be
regarded as indicating a t endency to increase. I n anot her animal
wi t h normal figures of 2 to 5 rag. t he first injection of phlorhizin was
followed by a rise to 11 mg., again a t endency to increase, but a second
injection in t he same animal showed no change. A t hi rd ani mal
showed no change follorcing two separate injections. Table I is
t he protocol of one animal.
352 EXPEI~ TMF.NTAL HYPERGLYCEMI A
TABLE I
Effect of the Subcutaneous Injection of Phlorhizin.
We i ght 1.2 ki l os.
Rabbif 1.
Hr. Blood Dias- Urine.
Date. blood sugar tase*
was per per
drawn, i00 cc. 100 cc. Albumin. Sugar.
1920 a. m. rag. rag.
~112 3 Negat i ve. Negat i ve.
Jul y 22- Aug. 7. . t I39 8
Aug. 12. . . 11.3
p.ff~.
1. 30 122 4
" 13 . . . . . . . . . 1. 30 131 9
" 14 . . . . . . . . . 1. 30 128 3
" 20 . . . . 11. 30
#. m.
1. 30 137 20
" 21 . . . . . . . . . 1. 30 128 9
" 22 . . . . . . . . . 1. 30 137 14
~.ffl.
" 30 . . . . . . . . 11. 30
1. 30 122 9
" 31 . . . . . . . . . [ 1. 30 115 2
Negat i ve. Negat i ve.
Positive. "
Positive. Negat i ve.
Positive. Positive.
Remarks.
Normal amounts witl
minimal and ma~ma
of six detcrmlnations
Phlorhlzin, 0.25 gm
subcut aneousl y.
Phl orhi zl n, 0.25 gm
subcut aneousl y.
Hi gh di ast ase probabl.~
due t o repeat ed bleed
h~s.
Phl or ~, 0.25 gm
subcutaneously.
* Throughout the tables "diastase" refers to the amount of sugar produced
by the action of the blood upon soluble starch.
Four rabbits were given uranyl nitrate in doses of 0.003 gin. of
pure salt. All four showed albuminuria and glycosuria, and all were
fatally intoxicated and showed acute nephritis at autopsy. None
of these showed hyperglycemia and none showed any increase in
diastatic activity of the blood even when moribund. Table I I is
the protocol of one animal.
Five rabbits were given doses of 0.080 gm. of morphine sulfate
subcutaneously. Collectively fourteen injections of morphine were
given. All showed some degree of hyperglycemia, three showed
H. T. KAR S NE R , H. L. KOE C KE R T , AND S. A. WAHL 353
glycosufia, and aU showed respiratory disturbance. A definite
increase in diastase occurred when severe hyperglycemia was pro-
duced. Table I I I is a protocol of one animal.
Six rabbits were given adrenalin (Parke, Davis and Company)
in doses of 2 cc. of 1:1,000 solution from a freshly opened bottle.
Collectively eight injections were given. All showed hyperglycemia
T ABL E I I .
Effect of the Subcutaneous Injection of Uranyl Nitrate. Rabbit 2.
Weight 1.1 kilos.
Date.
Hr. Blood Dias-
blood sugar tase
was per per
drawn. I00 cc. 100 cc.
1920 a. m. rag. rag.
~110 4
Aug. 25--Sept. 3. i ( 192 10
~ept . 17. 11. 00
" 18 . . . . . . .
" 19.
" 20 . . . . . . .
" 2 1 . .
" 2 2 . .
" 2 3 . .
" 2 4 . .
" 2 5 . . .
" 26. .
1~ . m .
1. 00 128 4
1. 00 125 4
1. 00 156 4
1. 00 172 6
1.00 185 8
1.00 140 7
Urge.
Albumin. Sugar.
Ne ga t i ve . Ne ga t i ve .
Ne ga t i ve . Ne ga t i ve .
Pos i t i ve.
" D. 3per cent .
" Ne ga t i ve .
Remarks.
No r ma l a mo u n t s wit]
ma x i ma l a n d mi n i ma
of si x d e t e r mi n a t i o n s
Ur a n y l ni t r a t e , 3 mg
s u b c u t a n e o u s l y .
Di ed. Ac u t e t u b u l a r
nephr i t i s .
and glycosuria. I n one animal wi t h control figures ranging between
4 and 6 rag. per 100 cc. t he first injection of adrenalin was followed
by a figure of 11 mg. for blood diastatic activity. All others showed
no increase. Table I V is a protocol of one animal.
Punct ur e of t he floor of t he fourt h ventricle was performed in
three animals, one by t he Claude Bernard met hod and two by t he
Eckhard met hod. All showed hyperglycemia, two showed gly-
354 EXPEI~TM-ENTAL HYPERGLYCEMIA
cosuri a, and none showed a ny defi ni t e i ncrease i n di ast at i c act i vi t y.
Tabl e V is t he pr ot ocol of one ani mal .
Seven r abbi t s were pl aced on di et s al t er nat el y of gr een vege-
t abl es and of car r ot s, oat s, and wat er . Ther e was no al t er at i on
TABLE III.
E~ect of the Subcutaneous Injection of Morphi ne Sulfate.
Weight 1.6 kilos.
Rabbit 3.
Hr . Blood Di as-
Dat e. blood sugar tase
was per per
drawn. 100 cc. 100 c c .
1920 a. m. rag. rag.
/125 3
July 20-Aug. 7. ~180 13
~ug. 11 . . . . . . . . . 8.30
10.30 320 16
" 12 . . . . . . . . 10.30 135 12
" 13 . . . . . . . . . i 10.30 125 9
" 19. .[ 8.30
10.30 419 35
" 20. .. 10.30 132 12
" 21. .. 10.30 139 6
" 30 . . . . . . . . . ~ 8.30
10.30 402 41
" 31.. 10.30 114 10
Sept. 1. .. 10.30 138 9
Urine.
Albumin. Sugar.
Negative. Negative.
Negative. Negative.
Negative. 1.5percent.
Negative. 1.8percent.
Remarks.
Normal amounts with
maximal and minimal
of six determinations,
Morphine sulfate, 2 cc,
of 4 per cent solution
(80 rag.) subcutane-
ously.
Morphine sulfate, 2 cc
of 4 per cent solutior
(80 rag.) subcutan6
ously.
Morphine sulfate, 2 cc
of 4 per cent solutior
(80 rag.) subcutane.
ous i y.
of bl ood sugar or of di ast at i c act i vi t y of t he bl ood. Tabl e VI is t he
pr ot ocol of one ani mal .
Two r abbi t s were bl ed r epeat edl y. The hemogl obi n .was ma r ke dl y
r educed. Unf or t una t e l y t he cell count s were not det er mi ned at t he
begi nni ng of t he exper i ment but t he fi gures gi ven i ndi cat e a mar ked
H. T. KARSNER, H. L. KOECKERT, AND S. A. WAHL 352
reduct i on. Associated wi t h the anemi a was an increase in bl ood
sugar, as has been found by Hirsch. There was also an increase in
di ast ase as i ndi cat ed in Tabl e VI I .
TABLE IV.
Ef f e c t o f t he S u b c u t a n e o u s I n j e c t i o n o f A d r e n a l i n Chl or i de.
Weight 1.8 kilos.
Rabbi t 4.
Da
July 2 6 -
Aug. 11.
" 12.
" 13.
" 19.
" 20.
" 21.
" 30.
" 31.
Sept. 1.
~ 2.
Urine.
Albumin. Sugar.
Negative. Negative.
Negative. 2.0 per cent.
" Negative.
Negative. 1.8 per cent.
Negative. 2.5 per cent.
u
1.7 " "
" Negative.
Remarks.
Normal amounts with
maximal and mini-
mal of six determi-
nations.
Adrenalin chloride, 2
cc. of 1:1,000 so-
lution subcutane-
ously.
Adrenalin chloride, 2
cc. of 1:1,000 so-
lution subcutane-
ously.
Adrenalin chloride, 2
cc. of 1:1,000 so-
htion subcutane-
ously.
Ni ne rabbi t s were definitely asphyxi at ed either by smot heri ng or
by placing t hem in t he Benedi ct ani mal cal ori met er under low
oxygen tension. I n one no hypergl ycemi a was produced; ill six
moder at e hypergl ycemi a resulted wi t h a t endency t o increase in t he
amount of bl ood diastase in two. I n t wo mar ked hypergl ycemi a wi t h
356 EXPEI ~I MFNTAL HYPERGLYCEMI A
TABLE V.
Effect of Puncture of the Floor of the Pourtk Ventricle.
Weight 1 kilo.
Rabbit 5.
Dat e.
1920
ept. 14-24..
~ct. 4..
" 10...
Hr.
blood
was
drawll.
11.45
1.45
1.45
1.4~
Blood
sugar
per
100 ec.
mg.
120
129
536
90
110
Di as -
tase
per
I 00 cc.
mg.
7
9
8
10
6
Urine.
Albumin. Sugar.
Negative. Negative.
Negative. 0.5 per cent.
" Negative.
Remarks.
Normal amounts with
maximal and mini-
real of three deter-
minations.
Bernard puncture of
floor of fourth ven-
tricle.
Died.
Weight 1 kilo.
TABLE VI.
Effect of Diet. Rabbit 6.
Dat e.
1920
July 21.
" 23 . . . . . . .
" 26.
" 30.
Blood
sugar
per
100 ce.
mg.
155
140
168
137
D iastase
per
100 cc.
mg.
8
5
4
5
Urine.
Albumin. Sugar.
Negative. Negative.
Rema~s .
After green vegetable die1
for 5 days.
After green vegetable die1
for 7 days.
After carrots, oats, an
water for 3 days.
After carrots, oats, anc
water for 7 days.
a def i ni t e i ncr eas e i n t he c onc e nt r a t i on of bl ood di as t as e was pr o-
duced. Ta bl e VI I I i s t he pr ot ocol of one r a bbi t .
Tot a l exci si on of t he pa nc r e a s was successf ul l y pe r f or me d i n t hr ee
dogs, one of whi ch l i ved 36 hour s, a not he r a bout 48 hour s, a nd a t hi r d
a bout 56 hour s . Al l s howed hype r gl yc e mi a , gl ycos ur i a, a nd ma r ke d
357
Urine. Blood Diastase
Date. sugar
per
per 100 ce.
100 c
1920 rag. rag.
3ct. 15-17. .
91 2
"" {.114 4
" 26 . . . . . . . 140 4
" 27. 125 7
" 28 . . . . . . . 100 3
Nov. 4 . . . . . . . . 97 4
" 5. 119 3
" 6. 115 3
" 12. 123 3
" 13 . . . . . . . 117 7
" 14 . . . . . . . 121 4
" 18 . . . . . . . 148 15
" 19 . . . . . . . 144 16
" 20 . . . . . . . 158 15
" 24 . . . . . . . 205 10
" 25 . . . . . . 205 15
Albumin. Sugar.
i
Negative. Negative.
H. T. KARSNER~ H. L. KOECKERT~ AND S. A. ~' AHL
TABLE VII.
Effect of Repeated Bleeding. Rabbit 7.
Wei ght 0.75 kilo.
Remarks.
Normal amount s wi t h
maxi mal and mi ni mal
of t hree det ermi nat i ons.
Aft er 9 days intermission.
After 7 days intermission.
After 6 days intermission.
Red blood cells 6,000,000;
hemoglobin (Sahli) 55
per cent.
After 4 days intermission.
Mt er 4 days intermission.
Red blood ceils 5,360,000;
hemoglobin (Sahli) 55
per cent.
" 26 . . . . . . . 163 13
TABLE VI I I .
Effect of Asphyxia. Rabbit 8.
Wei ght 1.2 kilos.
Urine.
Date. Remarks.
1921
Jan. 20 . . . . . .
" 21 . . . . . .
" 22 : . . . . .
Feb. 7 . . . .
" 8 . . . . . . .
Blood
sugar
per
I00 cc.
mg.
122
107
81
347
Diastase
per
100 cc.
mg.
4
7
4
19
Albumin. Sugar.
Negative. Negative.
Negative. 1.4 per cent.
Nor ma l .
Asphyxi at ed in Benedi,
t ank; low oxygen ter
sion for hr.
358 EXPERI MENTAL HYPERGLYCEMIA
increase in diastatic activity of the blood. The dog illustrated in
the protocol (Table IX) was free from general infection, one other
showed a slight general fibrinous peritonitis, and one showed gan-
grene of the duodenum. The results, however, were parallel in all
three animals.
Weight 11 kilos.
TABLE I X.
E f f e c t o f P a n c r e a t e c t o my . Do g 1.
Dat e.
19Z0
Nov. 18-22 . . . .
" 23 . . . . . . .
" 2 4 . . .
" 2 5 . . .
" 2 6 . . .
Hr .
blood
WaS
~rawn.
l l . O O I
1 . 0 0
9 . 0 0
11. 00
11. 00
Urine.
Albumin. Sugar.
Negat i ve. Negat i ve.
Negative. 2.3 per cent .
" 4.0 " "
" 5.0 " "
Remarks.
Nor mal amount s wi t h
maxi mal and mi ni -
mal of t hree det er-
mi nat i ons.
Complete pancreat ec-
t omy; finished 11
a . m.
Blood at close of oper-
at i on.
Blood 2 hrs. af t er
operat i on.
Blood 10 hrs. aft er
operation.
Blood 24 hrs. af t er
operation.
Blood 48 hrs. aft er
operation.
Ani mal found dead i n
cage.
* Th i s hi gh f i gur e was d e t e r mi n e d b y i de nt i c a l l y t h e s a me me t h o d as t he
ot her s . Th e o t h e r t wo a ni ma l s s howed ma x i mu m f i gur es f or bl ood s uga r of 416
a n d 540 rag. , a n d ma x i ma for di a s t a t i c a c t i vi t y of 53 a n d 31 mg.
Two dogs were completely anesthetized with ether for I hour.
A slight increase in blood sugar and in diastatic activity of the blood
was found; both of these were of short duration. In one animal
H. T. KARSNER, H. L. KOECKERT, AND S. A. WAHL 359
with control figures for diastatic activity of 3 to 13 mg. per 100 cc.,
the ether anesthesia was followed 10 hours later by a figure of 22 rag.
That this is not constant will be seen by reference to the protocol of
the animal in which enteroenterostomy was performed (Table XI).
The other experiment with ether is shown in Table X.
T A B L E X.
Effect of Ether Anesthesia. Dog 2.
Weight 10 kilos.
Btood
Dat e. sugar
per
100 cc.
19gO mg.
~105
Nov. 7--9 . . . . . . ~134
" 16 . . . . . . . 163
240
240
" 17 . . . . . . . 153
" 18 . . . . . . . 143
137
D i a ; a s e l
100 c c - -
13 "
14
12
18
8
5
8
Urine.
Albumin. Sugar.
Negative. Negative.
No urine.
Negative. Negative.
Remarks.
Normal amounts with
maximal and minimal
of three determinations.
Before anesthesia.
Ether " 9.30-
10.30 a.m. (1 hr.).
Blood 2 hrs. following
anesthesia.
Blood 10 hrs. following
anesthesia.
Blood 24 hrs. following
anesthesia.
Blood 36 hrs. following
anesthesia.
Blood 48 hrs. following
anesthesia.
A dog was subjected to lateral enteroenterostomy. The opera-
tion required 1 hour and was followed by an uneventful recovery.
Table XI shows that there was a tendency to hyperglycemia but no
increase in diastatic activity of the blood.
3 6 0 E XP E R ~ NT AL HYPERGLYCEMIA
TABLE XI .
Effect of Enleroenterostomy Operation. Dog 3.
We i g h t 12 ki l os,
Dat e.
Hr. Bl ood Dias-
blood sugar tase
was per per
drawn. 100 cc. 100 cc.
1920 a. r a. rag. trig.
Dec. 14-16. [ 89 8
[ 109 12
" 20 . . . .
12. 00 222 7
p.nt.
2. 00 161 $
12. 00 115 13
~.m.
" 21 . . . . . . . . 12. 00 119 5
" 2 2 . . .
" 23. . .
.~.mo
12. 00 136 4
a. m,
12. 00 130 6
12. 00 114 12
Urine.
Albumin. Sugar.
Negat i ve. Negat i ve.
Ne ga t i ve . Ne ga t i ve .
Negat i ve. Negat i ve.
Remarks.
Nor mal amount s wit
maxi mal and minims
of t hree det ermi w
tions,
Ent eroent erost omy
hr. dur at i on) .
Blood i mmedi at el y fo
lowing operation.
Blood 2 hrs. following
operation.
Blood 12 hrs. following
opexation.
Blood 24 hrs. followin~
operation.
Blood 36 hrs. following
operation.
B l o o d 4 8 hrs. following
operation.
B l o o d 7 2 h r s . f o l l o w i n g
operation.
I V.
SUMMARY.
Upon the subcutaneous injection of phlorhizin and uranyl nitrate,
their action being checked by the production of glycosuria, no
constant change was produced in the concentration of the blood
diastase. The adrenalin and puncture of the floor of the fourth
ventricle both produced a marked transitory hyperglycemia and
glycosuria without altering the content of blood diastase. On the
other hand, morphine, when producing a marked definite hyper-
H. T. K A R S N E R , H. L. K O E C K E R T , A N D S. A. W A H L 361
glycemia, caused also a decided increase in t he concentration of t he
blood diastase.
By varying t he di et of normal rabbits no material change was
produced in t he amount of blood diastase. By bleeding normal
rabbits periodically as carried out in t he experiments, there was no
effect upon t he diastatic act i vi t y until definite hemoglobinemia was
produced; t hen there was a t endency to increase in t he diastatic
cont ent simultaneously wi t h t he rise in blood sugar.
I n order to det ermi ne t he factors leading to t he increase in blood
diastase by t he injection of morphine, t he effect of asphyxia was
not ed. I n t he asphyxiated as well as in t he morphinized animals
when marked hyperglycemia was produced there resulted a decided
increase in t he concentration of t he blood diastase. We have no
ground for an opinion as to whet her or not morphi ne hyperglycemia
is due to asphyxia. All our morphinized animals showed respiratory
depression and i t appears at least possible t hat t he increase in diastatic
act i vi t y may have something in common with t hat of asphyxia.
Upon complete removal of t he pancreas in dogs t he hyperglycemia
and glycosuria were progressive unt i l deat h and were accompanied
by a definite decided increase in t he diastatic act i vi t y of t he Mood,
t he rise occurring at varying intervals following t he operation in
t he different animals; but in no way was t he increase in t he diastase
proportional to t he amount of blood sugar.
Except for a slight t endency to increase 12 hours following t he
anesthesia, t he ether anesthesia administered for 1 hour produced
no definite change in t he diastatic cont ent of t he blood, even t hough
a slight hyperglycemia was i mmedi at el y produced. The control
operation performed consisted in an ent eroent erost omy of 1 hour' s
duration, as a result of which t he diastatic cont ent was not changed
from t he normal. The slight hyperglycemia produced was undoubt -
edly t he result of ether anesthesia.
Wat anabe poi nt s out t he great vari at i on in t he diastatic act i vi t y
of t he blood of rabbits, which is also found in our experiments. The
same applies to t he dog. I n bot h animals t he normal diastatic
act i vi t y is greater t han t hat of man.
If it prove t rue upon more ext ended st udy t hat human diabetes
is associated wi t h an increase in diastatic act i vi t y of t he blood, as
362 EXPERIMENTAL HYPERGLYCEMIA
is indicated by the studies of Myers and Killian and of DeNiord and
Schreiner, it would seem t hat the experimental forms of this disease
produced by pancreatectomy and perhaps also by asphyxia and
morphine administration more nearly approximate the human disease
than do other forms of experimental hyperglycemia. I t is suggested
t hat when inferences are drawn from experimental studies of animals
these similarities and dissimilarities should be taken into consideration.
V.
CONCLUSIONS.
1. The diastatic activity of the blood is not materially changed by
the subcutaneous injection of phlorhizin, uranyl nitrate, or adrenalin.
2. The diastatic activity of the blood is not affected by puncture
of the floor of the fourth ventricle.
3. The diastatic activity of the blood is definitely increased by
subcutaneous injections of morphia when a marked hyperglycemia
is produced. The same phenomenon appears in asphyxia.
4. Complete pancreatectomy in dogs produces an increase in the
diastatic activity of the blood.
5. The diastatic activity of the blood is not altered by the diet.
6. Et her anesthesia, alone, produces a very slight tendency to
increase in the diastatic activity of the blood.
7. Repeated periodic small hemorrhages (4.5 cc.) produce no change
in the diastatic activity of the blood until a definite color anemia
results, when a slight tendency toward increase occurs simultaneously
with the rise in blood sugar.
8. The diastatic activity of the blood is not proportional to the
concentration of the sugar in the blood.
BIBLIOGRAPHY.
Allen, F. M., Studies concerning glycosuria and diabetes, Boston, 1913, 117.
Brown, H. L., Diabetes in relation to ductless glands, BriL Med. J. , 1920, ii, 191.
Folin, O., and Wu, H., A system of blood analysis, d. Biol. Chem., 1919, xxxviii,
81; Suppl ement I. A simplified and improved method for determination of
sugar, 1920, xli, 367.
Hirsch, E., Neue Ergebnisse fiber das Verhalten des Blutzuckers nach Ader-
l~ssen, Biochem. Z., 1915, lxx, 191.
H. T. K A R S N E R ~ H. L. K O E C K E R % A N D S. A. W A H L 363
Lewis, D. S., and Mason, E. H., The diastatic ferments of the blood, J. Biol.
Chem., 1920, xliv, 455.
MacLeod, J. J. R., and Pearce, R. G., Studies in experimental glycosuria.
V. The distribution of glycogenolytic fermer~t in the animal body, especially
of the dog, Am. J. Physiol., 1909-10, xxv, 255; VII. The amount of glyco-
genase in the liver and in the blood issuing from it, as affected by stimulation
of the great splanchnic nerve, 1911, xxviii, 403; VIII. The relationship of the
adrerml glands to sugar production by the liver, 1911-12, xxix, 419.
Milne, L. S., and Peters, H. Le B., Observations of the glycolytic power of the
blood and tissues in normal and diabetic conditions, Y. Med. Research, 1912,
xxvi, 415.
Myers, V. C., Chemical changes in the blood in disease, J. Lab. and Clin. Med.,
1919-20, v, 640.
Myers, V. C., and Killian, J. A., Studies on animal diastases. The increased
diastatic activity of the blood in diabetes and nephritis, I . Biol. Chem., 1917,
xxix, 178.
DeNiord, H. H. , and Schrein~er, B. F., Diastatic activity of the blood in cancer,
syphilis, and diabetes, Arch. l nt . Med., 1919, xxiii, 484.
Watanabe, C. K., The effect of the administration of various substances on t he
blood-diastase in rabbits, Am. J. Physiol., 1917-18, xlv, 30.