Effect of fasting on blood sugars in hereditary hypopituitary dwarf mice


Mirand, E.A.; Osborn, C.M.

Proceedings of the Society for Experimental Biology and Medicine 81(3): 706-708

1952


Hereditary hypopituitary dwarf mice of the Bar Harbor strain were fasted 12-96 hrs. and blood sugars recorded at intervals using modified Folin-Wu methods of Klendehoj-Hubbard. Normal mice of the same strain served as controls. Blood sugars of fed hereditary hypopituitary dwarfs are slightly but not significantly lower than in fed normals. Sugar content in the blood of fasting dwarfs drops sharply to 68 mg% at the 96th hr. as contrasted with 103 mg% in normal mice. The sensitivity of the dwarf to fasting is somewhat similar to that of hypophysectomized animals. This marked sensitivity of the hypopituitary dwarf may best be attributed to the known imbalance in the adrenal-pituitary axis and/or the deficiency of the pituitary growth factor in the dwarf.

Effect
of
Fasting
on
Blood
Sugars
in
Hereditary
Hypopituitary
Dwarf
Mice.*
(19995)
EDWIN
A.
MIRANDt
AND
C.
M.
OSBORN.:
(Introduced
by
Robert
Gaunt.)
From
the
Department
of
Zoology,
Syracuse
University,
Syracuse,
N.
Y.
706
Snell(1)
described.
in
a
strain
of
mice,
an
hereditary
dwarfism
which
behaved
as
a
true
Mendelian
recessive.
Since
then
many
inves-
tigations
have
been
carried
out
on
dwarf
mice
which
have
shown
interesting
morphological
and
metabolic
anomalies.
Snell
(1)
described
their
thyroid
deficiency
and
obtained
restora-
tive
effects
with
a
thyroid-stimulating
extract.
and
Smith
and
MacDowell(2)
showed
that
a
hypoplastic
condition
existed
in
the
acidophilic
cells
of
the
anterior
pituitary
-
lobe
and
in
the
sex
glands,
the
skeleton,
and
the
adrenal
cortex.
By
transplantation
of
the
anterior
pituitary
lobe
tissue
from
rats
to
dwarf
mice.
normal
growth
could
be
achieved
and
other
underdeveloped
structures
were
restored
to
normal.
Therefore.
they
concluded
that
this
dwarfism
was
the
result
of
an
hereditary
an-
terior
pituitary
deficiency.
hemp
(3.4)
showed
that
normal
growth
could
be
restored
by
re-
placement
therapy
with
anterior
pituitary
ex-
tract
and
with
growth
hormone.
MacDowell.
Laanes,
and
Smith
(5)
;
Dawson(
6)
:
Osborn
(7);
Marshak(8);
Boettiger
and
Osborn
(9)
:
Rouse
and
Osborn
(10);
Schonholz
and
Os-
born
(11)
;
Haack
(12)
;
Mirand
and
Osborn
(13);
and
other
investigators
have
all
re-
ported
observations
related
to
the
endocrine
or
morphological
abnormalities
of
the
hypo-
pituitary
dwarf
mouse.
Since
various
endocrine
glands
and
their
extracts
have
been
found
to
have
an
influence
on
metabolic
processes.
it
was
felt
that
the
hereditary
hypopituitary
dwarf
might
serve
as
an
excellent
animal
in
which
to
study
blood
glucose
values
associated
with
fasting.
Materials
and
methods.
The
animals
used
*
This
investigation
was
supported
in
part
by
a
grant-in-aid
from
the
National
Heart
Institute,
U.
S.
Public
Health
Service.
t
Present
address:
Roswell
Park
Memorial
Insti-
tute,
Buffalo,
N.
Y.
Present
address:
University
of
Buffalo,
Buffalo,
N.
Y.
in
this
study
were
hereditary
hypopituitary
dwarf
mice
of
the
Bar
Harbor
strain,
and
for
controls
normal
mice
of
the
same
strain
were
utilized.
All
dwarfs
were
9
to
12
months
old,
ranging
in
weight
from
9
to
14
g.
Normal
mice.
35
to
42
days
old,
served
as
controls,
since
their
weights
at
this
time
were
similar
to
the
dwarfs,
moreover,
at
this
age
the
nor-
mal
mice
are
developmentally
similar
to
the
dwarfs.
The
animals,
bedded
with
ground
corn
stalks
in
solid-bottomed
cages,
were
maintained
on
water
and
Purina
laboratory
chow.
The
temperature
of
the
animal
room
was
about
75
2
F.
Experiments
designed
to
determine
the
effects
of
fasting
and
nonfasting
upon
the
blood
sugar
level
of
normal
and
of
dwarf
mice
were
carried
out.
The
fasting
periods
used
ranged
from
12
to
96
hours,
as
indicated
in
the
accompanying
tables.
Blood
samples
for
sugar
determinations
were
drawn
after
10
p.m.
While
being
bled,
the
mice
were
held
gently
to
minimize
the
possible
effect
of
excitement
upon
the
blood
sugar
level.
Blood
for
all
sugar
analyses
(modified
Folin-Wu
methods
of
Klendehoj-Hubbard)
was
obtained
by
using
the
following
technic.
The
animal's
tail,
having
been
stroked
and
warmed
to
pro-
mote
vascular
dilation
and
blood
flow,
was
nicked
with
a
sharp
razor.
If
cut
properly
to
include
a
prominent
subcutaneous
blood
vessel,
large
drops
of
blood
quickly
form
but
the
tail
will
heal
promptly.
Fresh
blood
was
quickly
drawn
in
a
Sahli
pipette
and
any
ex-
cess
wiped
off
the
stem.
The
blood
was
then
chemically
prepared
and
the
colors
compared
in
a
Klett
colorimeter.
The
blood
sugar
values
obtained
are
consistent
relative
amounts
rather
than
absolute
ones.
Results.
Blood
sugar
determinations
on
fed
and
fasted
dwarf
and
normal
mice.
In
Tables
I
and
II
are
shown
the
average
blood
glucose
values
for
fed
dwarf
mice
with
normal
controls
and
for
dwarfs
and
normals
fasted
12
to
96
hours.
In
the
fed
state
the
average
FASTING
ON
BLOOD
SUGARS
IN
HEREDITARY
HYPOPITUITARISM
707
TABLE
I.
Effect
of
Fasting
on
Blood
Sugar
of
Normal
and
Dwarf
Mice.
Normal
Dwarf
Blood
Blood
No.
in
series
Hr
fasted
sugar,
mg
%
S.E.
No.
in
series
Hr
fasted
sugar,
mg
%
S.E.
t-value
10
155
-4-
4.26
21
0
143
-4-
4.96
.18'
50
12
147
-I-
2.21
15
12
110
-4-
3.13
10
is
15
128
-I-
2.23
10
15
105
-4-
2.81
6.38
37
16
123
-I-
1.82
15
16
100
-t-
4.56
6.21
28
18
119
2.21
15
18
94
4.35
5.10
18
21
124
-t-
2.47
10
21
95
-4-
3.98
6.17
50
24
133
±
2.18
15
24
93
2.98
10.81
12
27
131
2.56
15
27
97
-I-
1.82
12.50
30
30
137
2.23
15
30
92
-4-
5.08
8.03
24
40
138
-t-
3.36
15
40
88
-4-
2.68
11.36
12
48
117
-t-
1.23
12 48
75
-4-
1.71
21
12
72
112
-t-
1.44
12
72
71
-4-
1.87
17.91
12
96
103
-t-
1.03
12
96
68
-t-
1.86
15.90
Not
significant;
all
other
values
are
significant.
TABLE
IL.
Sequential
Blood
Sugar
Determina-
tions
of
lit
Normal
and
10
Dwarf
Mice
Subjected
to
Fasting.
Hr
fasted
Blood
saga
r.
mg
7
S.E.
,---Dwarf
Blood
sugar,
mg
%
S.E.
t-value
0
1.55
+4.3
143
ri-
5
.18t
12
149
±
2.2
108
-t-
2.1
13.66
15
126
.-1.-
3.1
102
-t-
1.8
6.66
18
125
.-1.-
5.•_>
97
-+-
1.9
5.09
24
1311
-,
1.2
92
-+-
2.2
11.51
23
129
-t-
3.1
95
-t-
1.5
9.71
fit;
134
-t-
1.8
91
-t-
2
16.54
27
133
±
2.1
88
-+-
1.6
17.30
28
135
±
1.4
90
±
1.6
20.45
29
133
±
2.5
89
±
1.2
15.71
30
13S
±
L3
92
.-1.-
3.3
12.22
3(i
131
±
2.7
87
±
2.5
11.89
4)
12S
±
!.9
85
-t-
3.6
8.69
*
Control
mice.
t
Not
significant
;
all
other
values
are
significant.
blood
sugar
values
for
the
dwarf
mice
(143
mg
%
)
are
slightly,
but
not
significantly,
lower
than
those
of
the
normal
mice
(155
mg
Jo
).
The
blood
sugar
level
of
the
fasting
dwarf
drops
most
precipitously
around
the
18th
hour.
followed
by
a
more
gradual
but
steady
decline
to
an
average
value
of
68
mg
%
after
96
hours
of
fasting.
In
contrast,
normal
mice
exhibit
the
greatest
blood
sugar
drop
between
the
12th
and
18th
hours
of
fasting,
followed
by
some
recovery
between
the
21st
and
40th
hours
of
fasting.
Thereafter,
a
grad-
ual
second
drop
occurs,
reaching
a
minimum
of
103
mg
%
at
the
96th
hour.
It
is
to
be
emphasized
that,
although
prefasting
blood
sugar
values
are
essentially
alike
for
dwarfs
and
normal
controls,
the
normal
mice
are
able
to
maintain
high
levels
rather
tenaciously
even
during
fasting,
while
dwarfs
exhaust
their
blood
sugars
steadily
and
rapidly.
Table
II
presents
the
average
blood
sugar
values
from
sequential
blood
sugar
determina-
tions
on
10
normal
and
10
dwarf
mice
sub-
jected
to
fasting
for
12
to
40
hours.
Sequen-
tial
determinations
represent
blood
sugar
analyses
on
a
series
of
blood
samples
taken
from
the
same
mouse
at
intervals
indicated
during
the
fasting.
These
data
are
in
close
agreement
with
the
results
in
Table
I,
despite
the
difference
in
sampling.
It
is
clear,
there-
fore,
that
dependable
values
may
be
obtained
when
multiple
blood
samples
are
taken
from
the
same
animal.
These
findings
show
the
sensitiveness
of
the
dwarf
to
fasting
to
a
de-
gree
that
the
dwarf
symptoms
resemble
the
observations
of
others
reported
for
hypophy-
sectomized
animals.
Although
in
the
dwarf
a
progressive
decrease
in
the
blood
sugar
level
occurs,
this
decline
is
not
associated
with
hypoglycemic
convulsions
and
death,
con-
trasted
with
hypophysectomized
animals
which
may
succumb
if
fasted
for
only
24
hours(14).
In
the
fasting
dwarf,
activity
is
curtailed
progressively
until,
by
the
end
of
the
96-hour
fast,
the
dwarfs
are
either
extremely
lethargic
or
dead.
In
this
study
about
one-
third
of
the
dwarfs
expired
by
the
96th
hour
despite
efforts
to
elevate
the
blood
sugar
by
administering
5%
glucose
by
stomach
tube.
708
FASTING
ON
BLOOD
SUGARS
IN
HEREDITARY
HYPOPITUITARISM
starvation
effects
were
not
superficially
dis-
cernible
in
normal
mice
at
the
end
of
the
96-
hour
fast.
Discussion.
When
hypophysectomized
ani-
mals
are
fasted,
they
suffer
unusually
rapid
losses
of
body
carbohydrates.
As
seen
in
this
study,
the
dwarf
mice
behave
somewhat
like
hypophysectomized
animals
in
that
after
a
fast
of
96
hours
the
blood
sugar
level
of
the
dwarf
is
considerably
lower
than
that
of
nor-
mal
animals.
It
is
generally
agreed
that
the
secretion
of
the
adrenal
cortical
steroid
hor-
mones
is
largely
controlled
by
anterior
pitui-
tary
adrenocorticotrophin
(ACTH).
The
dwarf,
representing
a
hypopituitary
state,
is
deficient
in
ACTH
(12
).
It
may
be
suggested,
therefore,
that
the
hypoplastic
condition
of
the
anterior
pituitary
and
the
adrenal
cortex
in
the
dwarf
is
associated
with
functional
de-
ficiencies
of
hormones
which
are
normally
con-
cerned
with
the
metabolism
of
carbohydrates.
This
imbalance
in
the
adrenal-pituitary
axis
in
the
dwarf
might
best
explain
the
severe
hypo-
dycemia
which
develops
under
the
stress
of
fasting.
However,
in
the
light
of
the
researches
of
Houssay
and
Anderson
(15),
and
De
Bodo
al.(16)
relating
the
growth
hormone
to
car-
bohydrate
metabolism,
it
is
not
unlikely
that
the
unique
blood
sugar
pattern
found
in
the
fasting
dwarf
mouse
may
be
partly
explained
by
the
animal's
deficiency
in
growth
hormone.
Experiments
designed
to
gain
information
on
this
problem
are
in
progress.
Summary.
Under
the
experimental
condi-
tions
employed,
findings
may
be
summarized
as
follows:
1.
Average
blood
sugar
values
for
fed
hereditary
hypopituitary
,
dwarfs
are
slightly,
but
not
significantly,
lower
than
those
of
fed
normal
mice.
2.
The
blood
sugar
level
of
fasting
dwarfs
drops
precipitously
to
a
minimum
of
68
mg
%
after
96
hours.
In
contrast,
normal
mice
exhibit
a
lesser
drop,
followed
by
some
recovery
which
later
gives
way
to
a
minimum
average
of
103
mg
%
after
96
hours
of
fasting.
3.
These
findings
show
that
the
sensitiveness
of
the
dwarf
to
fasting
is
somewhat
like
that
reported
for
hypophysectomized
animals.
This
sensitivity
herein
reported,
as
judged
by
the
severe
hypo-
glycemia
which
develops
under
the
stress
of
fasting,
might
best
be
attributed
to
the
known
imbalance
in
the
adrenal-pituitary
axis
in
the
dwarf.
1.
Snell,
G.
D.,
Proc.
Acad.
Sci.,
1929,
v15,
733.
2.
Smith,
P.
E.,
and
MacDowell,
E.
C.,
Anat.
Rec.,
1930,
v46,
249.
3.
Kemp,
T.,
Acta
Path.
et
Microbiol.
Scandanov.,
1933,
v16,
189.
4.
,
Acta
Path.
et
Microbiol.
Scandanov.,
1939,
v37,
290.
5.
MacDowell,
E.
C.,
Laanes,
T.,
and
Smith,
P.
E.,
9.
Boettiger,
E.
G.,
and
Osborn,
C.
M.,
Endocri-
nology,
1938,
v22,
447.
10.
Rouse,
C.
A.,
and
Osborn,
C.
M.,
Anat.
Rec.,
1948,
v101,
67.
11.
Schonholz,
D.
H.,
and
Osborn,
C.
M.,
Anat.
Rec.,
1949,
v105,
125.
12.
Haack,
M.
E.,
Thesis,
Syracuse
Univ.,
1950.
13.
Mirand,
E.
A.,
and
Osborn,
C.
M.,
Anat.
Rec.,
1951,
v109,
379.
14.
Houssay,
B.
A.,
New
England
J.
Med.,
1936,
v214,
971.
15.
Houssay,
B.
A.,
and
Anderson,
E.,
Endocri-
nology,
1949,
v45,
627.
16.
De
Bodo,
R.
C.,
Kurtz,
M.,
Ancowitz,
A.,
and
Kiang,
S.
P.,
PROC.
SOC.
EXP.
BIOL.
AND
MED.,
1950,
v74,
524.
Received
October
2,
1952.
P.S.E.B.M.,
1952,
v81.
Carnegie
Inst.
of
Washington
Yearbook,
1932,
v31,
47.
6.
Dawson,
A.
B.,
Anat.
Rec.,
1935,
v64,
7.
Osborn,
C.
M.,
Endocrinology,
1938,
8.
Marshak,
A.,
Am.
J.
Physiol.,
1939,
485.
v22,
v125,
370.
457.