The role of the cortical and cerebral layers of the adrenal glands in mobilizing carbohydrate and fatty resources in response to the effect of an extreme stimulant was investigated. It is shown that following adrenodemedullation and adrenalectomy, the leading role is played by the secretion of the adrenal medullary layer, whereas the role of suprarenals in the mobilization of fats is only slightly pronounced

Khechninashvili, G. G.

English

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NASA TECHNICAL iIEMORANDUM
	
NASA TM-75974
ROLE OF ADRENALS IN THE. MOBILIZATION OF CARBOHYDRATE
AND FAT RESOURCES AFTER OVERSTIMULATION OF RATS
C. C. Khechninashvili
Translation of "Rol' nadpochechnikov v wobilizatsii uglevodnvkh i
zhir"vvkh resursov pri chrezvvchavnom razdrazhenii krys", Farmakologiya
i ToksiKologiya, Vol. 35, No. 5, 1972 pp. 575-580
(NASA-Td-75974)
	 PCLE CF AGRESALS IN IRE
	 b80-12556
50BILIZATIGB OF CAPBChYCPAZE ANL FAT
PESOUCES AFTER CYEPS1IMU1A11CN CF PATS
(National Aeronautics and SFace
	 BncIasAd n inistraticr.)
	 13 p BC AC2/CF A01 CSCL 06C 63/51 18021
NATIONAL AERONAUTICS AND SPACE A1)^IINISTRATION
WASHINGTON, D. C. 20546	 3ANUARY 1980
UDC 612.015.32:612.397.21-06:612.45.018
ROLE OF ADR0ALS IN THE MOBILIZATION OF CARBOHYDRATE AND FAT RESOURCES A W
OVERSTDULATION OF RATS
By G. G. Hhec-hinashvili, Group of Neural- Endocrinology (Head-+Doctor of
Medical Sciences V. Ye. Ryzhenkov), Department of Pharmacology (Head —
Academician of USSR Academy of Medical Sciences, Professor S. V. Anichkov)
of the Institute of Experimental Medicine of the USSR Academy of Medical
Sciences, Leningrad
Adrenodenedullation and adrenalectamy in rats greatly
hampers the rise of the blood plasma glucose concen-
tration in response to immobilization. The liver gly-
cogen content subsides in these animals to a much
greater degree than in intact ones. Adrenodenedullation
and adrenalectamy do not eliminate the adipokinetic
action of immobilization. In mobilization of the blood
sugar following extraordinary irritation (overstimul.ation)
of rats, the leading part is played by the secretion of
the adrenal medullary layer, whereas the role of supra-
renals in the mobilization of fats is only slightly pro-
nounced.
Glucose and free (nonesterified) fatty acids ('A free fatty acids)
	
/57-'`
are the main energy resources of the organism. Theis mobilization respec-
tively from glycogen of the liver and ariglycerides of the fatty depots when
the organism is affected by stimulants has been established by a number of
authors (Selye, 1950; Engel and Fredericks, 1957; S. M. Leytes an3 Chzhou-su,
1962; Friedberg et al., 1963; V. Ye. Ryzhenkov et al., 1968; N. G. Nikul'cheva
and V. Ye. Ryzhenkov, 1970). The participation of the sympathetic nervous
*Numbers in margin indicate pagination in original foreign text.
1
4
system, adrenalin of the adrenal elands and a number of other hornmaial
factors is assumed in the mechanism of these reactions (Havel and Goldfien,
1959; Shafrir et al., 1960; S. M. Tjeytes and Chzhou-tisu, 1962; Lebowitz,
1965; Goodman, 1969; N. G. Nikul'cheva and V. :e. Ryzhenkov, 1970; Goth,
1971). The question of the value of secretion of the adrenal gland in these
processes has been studiad much less.
In this work a study was made of the role of the cortical and cerebral
layers of the adrenal glands in mobilizing carbohydrate and fatty resources
in response to the effect of an extreme stimulant. Lmxobilization of rats
was used as the latter; as is known immobilization produces considerable
change in the activity of the nervous and endocrine systems and results in
a whole series of biochemical changes in the organism (Brodie and Hunson,
1960; S. V. Ardchkov and I. S. Zavodskaya, 1965; V. Ye. Ryzhenkov, 1968 et
al.).
Methods of Study	 /576
The experiments were conducted on 350 satiated male rats weighing 180-
200 g. The animals were immobilized by fixing them in a stand for different
periods: 10, 30 minutes, 1 and 3 hours. Immediately after i.m obilization
the rats were decapitated. The concentration of total 11-hydroxycorticosteroids
(11-HXC) in the blood plasma was determined fluarometrically (I. Ya. Usvatova
and Yu. A. Pankov, 1968), free fatty acids in the plasma--by the colorimetric
method (Itaya w-0 Ui, 1965), glucose in the plasma--also color imetrically:
by the glucose-oxidase and for comparison the ortho-toluidine methods (E. G.
Tebneva aryl G. I. Saburova, 1970). The glycogen in the liver was analyzed
2
by a modified iode method of Krisman U. V. VysochirAa et al., 19k'8) . Adrena-
lectnny was carried out 36--48 hours before the experiment. After adrenalec-
tcmy the rats received 1% solution of sodium chloride to drink. A r=ber
of the animals were given minimum doses of hormones (directly before the
operation 2.5 mgfkg of desoxyeorticosterone-acetate (DOCA) intramuscularly,
one hour before the experiment 2.5 mg/kg DOCA, and 25 gAg of dexamethasone
intraabdaminally). Another part of the adrenalectimized rats entered the
experiment without supporting therapy. Denedullation of the adrenal glands
was carried out one month before the experiment by removal of the cerebral
layer with a special spoon. Cca plete removal of the cerebral and preser-
vation of the cortical layers of the adrenal glands were checked histolog-
ically after the experiments. The results of the experiments were statis-
tically processed (M. L. Belen'kiy, 1963).
Results
 and Their Discussion
The table presents the studied indices of carbohydrate and fatty metab-
olism after different periods of immobilization in the intact and operated
on animal and rats who were given DOCA and dexamethasone.
It is apparent that the hyperglycemic reaction to immobilization in the
intact rats developed already in the early periods of stimulation (10 minutes)
and the concentration of glucose in the blood plasma was high during all the
studied periods of immobilization. This was accompanied by intensified
glycogenolysis in the liver. The glycogen content in the liver was prog-
ressively reduced with an increase in the periods of immobilization.
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5
As follows from the table aarenodemedullation and adrenalectomy to a
considerable degree disrupted the hypuxglycemia react= to the extreme
stimulation. A tendency was merely noted for an increase in the £cigar
content in the blood plasma in the early periods of immobilization, which
apparently was linked to the extra-adrenal activity of the sympathetic
nervous system (S. M. Leytes and Chzhou-su, 1962). In the experiments on
the adrenalectonized animals without substitution administraLi n of small
doses of corticosteroids it was established that after 3-hour immobilization
there was considerable reduction in the concentration of sugar in the plasma.
In the adrenalectar zed rats maintained with small doses of hormones this
effect of mobilization was considerably less pronounced (see table). Similar
action of the corticosteroids administered to the adrenalectaaized rats has
already been noted in the literature (Engel and Fredericks, 1957).
That fact that suppression of the hyperglycemic reaction to the stimulus
was observed not only in the adrenalectamnized, but also in the adrenodemedul-
lized animals indicates the leading role of secretion of the cerebral layer
of the adrenal glands in increasing the level of sugar in the plasma.
In the operated on (especially the adrenalectonized.) animals as compared
to the intact during prolonged immobilization a considerably more pronounced
decrease was observed in the glycogen content in the liver, almost. complete
exhaustion of the carbohydrate supplies. Similar results were obtained
previously in our section N. V. Korkhov, 1970). It should be noted that
adrenalectomy reduced also the initial level of glycogen in the liver, while
during demeduJktion of the adrenal gland such an effect was not noted (see
6
table). Apparently this is explained by the action of the gluc000rticoids
on neoglucogenes . # The latter is confirmed by the results of our experi-
ments with administration of synthetic glucocorticoi.d,dexamethasone to intact
animals, as well as by the experiment to investigate the ll HXC content in
the blood plasma.
As is apparent from the table the administration of dexamethasone to
	
/579
intact animals resulted in the increase in the initial concentration of
glucose in the plasma and i.ntens^ fication of the hyperglycemic reaction to
immobilization. Two-fold administration of dexameibasone Was acoapanied
also by a considerable increase in the glycogen content in the liver and a
certain reduction in the degree of its decrease during immobilization.
A distinct increase in the 11-HXC level in the plasma was observed
already by 10 minutes of immobilization in which the maxim n by 30 minutes.
The 11-HXC level in the plasma remains high even in the later periods of
immobilization. In the adrenodemeduMized animals the reaction of the adrenal
cortex to immobilization was as well pronounced as in intact (see the figure).
Adn nistration of mineral-oorticoid dezoxyoorticosteroid did not reproduce
any of the studied effects of dexamethasone(see table).
The concentration of free fatty acids in the plasm of intact rats
exposed to immobilization, in the same way as glucose, increased already in
10 minutes. In contrast to the concentration of sugar in the plasma it
sharply increased after 3-hour stimulation. This lipo-mobilizing effect
was not significantly altered either by adrerbalentied Mation or adremlectomy
(see table). In the adrenalectcudzed rats who received a supporting dose of
7
'	 A	 C	 O
30
?S	 e
10	 ;i
if
/0
f_
/ 7 3 4 9 4 / 1 j= 11 J 4
Figure. Effect of Different Periods of Immobilization on Level of Total 11-
Hydroxycorticosteroids (11-MC) in Plasma of Intact (A), Adrenode-
rradultized (B) and Adrenalectomized Rats Without Administration of
Haimones (C) and After Administration of Hormones (D) .
On vertical--concentration of 11-HXQ (in Ng%). Light columns—
control; dark--after immobilization for 10 minutes (1), 30 minutes
(2), 1 hour (3), 3 hours (4), confidence boundaries computed with
D=0.05. A--in control and experimental groups of 20 animals; B, C,
D--5 animals
DOCA and dexametha.sone and in the animals that did not receive these hormones
the differences in the liver of the adipokinetic reaction to the employed
effect was not observed.
The lipo mobilizing effect of immobilization was implemented, apparently,
as a result both of the increase in the activity of the sympathetic nervous
system (Havel and Goldfien, 1959 et al.), and the extra-adrenal lipolytic
effect of ACTH (Lebowitz and Engel, 1965; Lebowitz, 1965; N. G. Nikul'cheva
and V. Ye. Ryzhenkov, 1970; Desbals et al., 1970), and possibly with the
participation of other hormonal factors (Goodman, 1969; Goth, 1971).
Thus, the results of the conducted experiments indicated that in imple-
menting the hyperglycemic reaction emeLging during immobilization of rats
8
the leading role belongs to secretion of the cerebral layer of the adrenals.
Here the value is revealed of the cortical layer of the Adrenal glands since
injection of small doses of corticosteroids prevents the pronounced decrease
in the glucose role in the blood plasma observed in adranaliectamized rats
after 3-hour immobilization.
In mobilization of the fatty resources the role of the adrenals is less
pronounced. Despite the well known lipolytic action of adrenali.n (Havel and
Goldfien, 1959; Goodttan, 1969 et al.), as well as the fact that injections
of dexamethasone resulted in a considerable increase in the pFA content in
the blood plasma (see table), in our experiments the adipokinetic action
	 /580
of immobilizEtion was observed both in the adrenodenedultzed and in the
adrenalectomized animal. However in the implementation of this effect in
the adrenalectamized rats that residual quantity of corticosteroids that
was recorded in the blood plasm in our experiments 1 1/2-2 days after
removal of the adrenal glands could have a permissive effect.
Conclusions
1. A leading role in the hyperglycemic reaction '-o an extreme stimulus
belongs to the secretion of the cerebral layer of the adrenal glands.
2. Injections of dexamethasoneresult in considerable increase in the
c:ontznt of free fatty acids in the blood plasma. At the same time the
adipokinetic effect is well pronounced in km-cbilization both in adrenode-
medulhzed and adrenalectanizud rats.
9
1. Anichkov, S. V.; and Zavodskaya, I. S. Fa 	terapiya yarmimcy loo ezni
("Pham alogical Therapy of Peptic Ulcers"], Leningrad, 1965.
2. Belen'kiy, M. L. lemen koliches 	 Q
effekta [ "Elements of Quantitative Evaluation of Phanraoological Effect"],
Leningrad, 1963.
3. Vysochina, I. V.; Kaverina, V. F.; and Konstantinova, I. N. Labor, Delo,
No 12, (1968), p 743.
4. Korkhov, V. V. author 's abstract of doctoral dissertation, Leningrad,
1970.
5. Leytes, S. M.; a.-id Ch4m-su, Vopr. sod. khimii, No 3, (1962), p 289.
6. Nikul'cheva, N. G.; and Ryzhenkov, V. Ye. in Reaulvatorn va
_ fui-ktsiya
biggenn_ykh aminov [ "Regulatory
 Function of Biogenic Amines"], Leningrad,
1970, p 82.
7. Ryzhenkov, V. Ye. Farmkol. i toksikol. No 5, (1968), p 545.
8. Ryzheukov, V. Ye.; Isachenko, V. B.; Nikul'cheva, N. G. at al. in Deystviye
neurotorr vkh sredsty na ngnMIEN gQ
	 al'nuyu_regulyatsiyu [ "Effect
of Neurotropic Resources on Neural and Hormonal Regulation"], Leningrad,
1968, p 164.
9. Tebiyeva, E. G.; and Saburava, G. I. inrovannyye nw^
	 klinicheskikh
i lavoratornykh issledWaqi
	Methods of Clinical and laboratory
Studies"], ed. V. V. Men'shikova. Biokhimicheskiye metody (Biochemical
Methods], Moscow, 1970, No 1, p 67.
10.Usvatova, I. Ya.; Pankav, Yu. A. in She metod ( redeleniya
Steroidnykh go=== v biologichsskikh zhidkostyakh I'Modern Methods of
Detemining Steroid Hormones in Biological Liquids"], Moscow, 1966, p 38.
11.Brodie, B.; and Hunson, H. •Caastroenterolocy, 1960, vol 38, p 353.
12.Desbals, B.; Desbals, P. and Agid, R. in the book: By B. Jeanrenaud, D.
Hepp Ed. WjWse Tissue, Relation and Metabolic Functions, London, 1970,
p 28.
	 _	 .-	
_	 _...
13.Engel, F. L.; Fredericks, J., Proc. Soc. Exp. Biol. (N.Y.), 1957, Vol 94,
p 593.
14.Friedberg, S. J.; Sher, P. ; Bogdonoff, M. D. at al., T Laid. Rgs:, 1963,
vol 4, p 34.
20
A
15. G- i-man, R. M. and Gual, B. C. , Ed. Yrogress in Endocrino` off, Amsterdamn,
1969, p 115.
16. Goth, E. B., E. Goth, J. Fovenyc (pda). Pol^tide Ho=wm. Metab.,
Budapest, 1971, p 165.
17. Havel, R. J. and Goldfien, A. J., Lipid Res., 1959, Vol 1, p 102.
18. Itaya, K. U., J. Lipid. Res., 1965, vol 6, p 16.
19. Lebowitz, H. E. in the book: Proceed. Seocncl International Congress
, Amsterdam, 1965, part II, p 1231. 	 --
20. Lebowitz, H. E. and LYgel, F. L., in the book: Handbook of Physiology
Washington, 1965, p 541.
21. Selye, H. Physiology and Pathology of Exposure to Stress, Montreal,
1950, p 116 and p 124.`	-- ---
22. Shafrir, E.; Sussman, K. E. and Steinberg, D., J. Lipid. Res., 1960,
vol 1, p 459.
11
I


Role of adrenals in the mobilization of carbohydrate and fat resources after overstimulation of rats

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