Review of Prof. B. K. Anand's Scientific Study

29 Pages·2012·23.57 MB·English

Indian J Physiol Pharmacol 2001; 45 (3):269-295
REVIEW ARTICLE
REVIEW OF PROF. B.K. ANAND'S SCIENTIFIC STUDY FIFTY YEARS
FOLLOWING HIS DISCOVERY OF FEEDING CENTRE
H. N. MALLICK
Department of Physiology,
All India Institute of Medical Sciences,
Ansari Nagar,
New Delhi - 110 029
(Received on March 8, 2001 )
Abstract : Prof. BK Anand the living legend, is the founder of modern
neurophysiology in India. His career spanned an era that marks the
beginning of Brain Research in India. His contributions to understanding
of brain functions began with the epoch making discovery of lateral
hypothalamic area as the 'feeding center'. Subsequently it encompasses a
wider range of studies from elucidation of the intricate mechanisms
underlying ingestive behaviour to hypothalamic regulation of
cardiovascular, respiratory, gastrointestinal activity and regulation of
various physiological functions by limbic system. The following review
gives an account ofthe contributions made by Prof Anand and his colleagues
during twenty five years ofhis illustrious career. The publications resulted
from his studies has not only stood as a testimony to understanding of the
neural control of ingestive behaviour and limbic functions but also have
been a sources of a great interest to those who pursue knowledge in this
field.
Key words: feeding centre lateral hypothalamic area
limbic system yoga
INTRODUCTION hypothalmic neurons under an ERATO (a
national programme ofJapan) project. I had
When asked to write an account of the the opportunity to come in close contact with
work of Prof. BK Anand on the eve of 'Fifty him when he was invited by Prof. Masao
years of discovery of feeding center', my Ito along with other living legends in
response was to say yes immediately. Neuroscience to adore the opening ceremony
Though I still enjoy the continued teaching of Fourth IBRO World Congress of
ofProf Anand which he does without respite Neuroscience in Kyoto in 1995. His
my realisation about his contribution to remarkable career in neurophysiology
neuroscience began when I was keenly spanning a period of twenty five years,
referring his studies while studying stands as a monument of unstinting efforts
neuronal plasticity of ventromedial to unravel the mystery ofhypothalamus and
270 Mallick Indian J Physiol Pharmacol 2001; 45(3)
limbic system underlying behaviour. During higher levels of the central nervous system,
this exceptionally productive career many the Department had various sections and
contributions were made '.. not only to research workers studying these by using
understand neural mechanism underlying different experimental techniques.
ingestive behaviour but also hypothalamic
regulation of cardiovascular, respiratory, While going there, the main objective
gastrointestinal activities and regulation of Dr Anand had, was to learn these various
.various physiological functions by limbic experimental techniques, which will enable
system. The much existing knowledge of him to set up a neurophysiology laboratory,
on return to India. However, as luck would
neural control ofingestive behaviour to day;
have it, while studying the use ofstereotaxic
even the sensational discovery of new
techniques, he discovered the presence of
hypothalamic peptide 'orexin' finds a root
two opposing mechanisms in the
in the resulting publications of Prof Anand.
hypothalamus regulating feeding behaviour,
The review described below gives an account
which at that time was considered to be an
of the contributions made by Prof. Anand
epoch making discovery. Till that time other
and his illustrious colleagues in the field of
workers had shown that ablation of the
brain research in India.
medial hypothalamic area of median
eminence resulted in overeating leading to
Dr. Anand joined as Professor of
obesity in rats for which mechanism, no
Physiology at the Lady Hardinge Medical
concrete suggestion was available at that
College, New Delhi, in 1949. Although he
moment. Dr. Anand while confirming this
had worked as a junior and middle level
also demonstrated that ablation of the
teacher in Physiology since 1943, all this
lateral hypothalamic area in the same
time he had not undertaken any research
region produced the opposite effect of
worth the name: his time being mostly
complete "Aphagia". With further
devoted to teaching and besides there being
experimental evidence he designated the
no facilities and infrastructure to do
lateral hypothalamic area as the "Feeding
research.
Center", providing urge to eat and the
medial area as the "Satiety Center"
In 1950, he was awarded Post-Doctoral
Training Fellowship by the Rockefeller producing satiation.
Foundation for one year. As he had been
personally interested to understand the So his stay of one year at the Yale was
functions of the Higher Nervous System, he devoted not only studying the different
decided to go for such training in the investigative experimental techniques but
Department ofPhysiology ofYale University also sometime on further studying the
School of Medicine. The department was feeding behaviour.
then. headed by Prof J.F. Fulton, who was
considered to be· one of the top most On return to India in 1952, he seriously
neurophysiologists ofthe world at that time. devoted his time to undertake various types
Under his personal interest in the of research. He could start the work
functioning of the various regions of the immediately on returns, as he was able to
Indian J Physiol Pharmacol 2001; 45(3) Fifty Years Following Discovery ofFeeding Centre 271
bring with him from USA a stereotaxic Dr Anand's most productive colleagues
apparatus, a stimulator, an ablating included especially Sheel Dua Sharma,
apparatus and a single beam oscilloscope G. S. Chinna, K. N. Sharma, S. K.
with its pre-amplifier. Manchanda, Usha Nayar and T. Desiraju.
Prof. Baldev Singh participated in all of the
A number of research studies and laboratory research. So the credit for the
projects in the field ofNeurophysiology were research studies conducted, deserved in this
undertaken at first during Dr Anand's stay write up is in the words of Dr Anand, "not
at the Lady Hardinge Medical College and of me alone, but is to be equally shared with
later on at the All India Institute of Medical my other colleagues".
Sciences, New Delhi. In addition to
the institutional facilities and grants, A reader may point out two deficiencies
this research was supported by the in this write up. Firstly, that there were
establishment of "Neurophysiology various similar studies being, carried out
Research Unit" of the Indian Council of during that period at various centres in
Medical Research. Thus a 'School of other countries also and there is no mention
Neurophysiology' probably the first of its of them in this. Secondly, many other
kind in India was started, where studies studies have been carried out on these
were undertaken by the introduction ofnew mechanisms even after 1973 with
experimental techniques with the objectives experimental techniques some confirming
of study of the "Brain and Behaviour" in the conclusions given here, while some
India. The techniques used, included the others providing a different concept ofthese
stereotaxic placement of electrodes for functions. Here is quoted an often repeated
making local electrolytic lesions, for statement of Dr Anand that, "Observations
electrical stimulation and for recording of made from any experiment are never wrong,
depth EEG, evoked potentials, and single it is the conclusions drawn from the same
unit potentials with microelectrodes. These which may change". Anyway, these
also permitted the use of unanaesthetised omissions have been intentional as the
and freely moving animals for behavioural whole objective of this write up was to
experiments. Using these techniques the highlight only the studies carried out by Dr
hypothalamic and limbic systems were Anand and his colleagues, in his laboratories
investigated to understand their roles in the under his guidance and direction.
'homeostatic' regulatory mechanisms of
visceral and behavioural functions. RESEARCH
Naturally, in these studies priority was
attached to understanding in more details As stated earlier Dr Anand's interest and
the new physiological mechanism regulating career in research began only when he went
the 'feeding behaviour'. A large number of for training in the discipline of
post-graduates, research scholars and Neurophysiology to Yale University in USA
colleagues were trained in this School, some in the year 1950. His year's stay there was
ofwho later on became leading contributors utilised in carrying out a small project
to neurophysiology in the country. Some of leading to the discovery of the presence of
272 Mallick Indian J Physiol Pharmacol 2001; 45(3)
Feeding" and "Satiety" centres in the on the regulation of one such function i.e.
hypothalamus. In addition he devoted many feeding bevaviour, which is vital, because
time in mostly learning the various it maintains energy balance in the body.
experimental techniques employed for the
study of eNS. This training allowed him to (1) NERVOUS REGULATION· OF FEEDING
use some of these techniques and BEHAVIOUR
experimental procedures for the valid
research studies undertaken by him and his Innate behaviour of feeding is
colleagues on his return to India. genetically fixed and is characteristic ofthe
species. The 'motivated' behaviour of
Some of the more important research from feeding depends upon the opposed 'drives'
Dr Anand's laboratory is summarised as of hunger and satiation, which are elicited
follow: and reduced directly by changes in the
internal environment and are thus
During a period of some 20 years, they "homeostatic" in nature (8). Most basic
studied the functional importance of those motivational forces on drives depend upon
regions of the brain, collectively designated central nervous regulation state; this is true
as the "limbic system". It is a system that also of feeding behaviour (9).
regulates various autonomic, visceral,
endocrine and behavioural functions of the (i) Maintenance of Energy Balance
individual, and thereby maintains normal
"homeostatic" conditions in the body Energy balance is brought about by
including the constancy of the "milieu adjustment offour important variables; food
interiuer" (1~7). Keeping this in view, the intake, stored energy, work, and heat
limbic system has also been designated as production. All these variables are
the "visceral brain". The hypothalamus, controlled by central nervous mechanisms
being the effector organ ofthis system, came similar to those that regulate other visceral
to be gradual recognition of the functional and endocrinal activities, so as to achieve
importance ofthose areas in the brain which constancy of the milieu interieur (10,11).
subserve autonomic functions, because they
form the structural background, not only of In maintaining a proper equilibrium,
emotional expression, but also of effective food intake has to be integrated with the
and motivated behaviour in the broadest other three variables, i.e. work done, heat
sense. This recognition can be considered produced, and energy stored. Ordinarily,
as a landmark in the history of medical the energy stored in the fat depots of the
science. body does not change appreciably. over long
periods, and body temperature is maintained
Although Dr Anand's Research Unit at normal levels by adjusting the heat loss
have analyzed various patterns ofregulation to heat production. In such situations food
from the Limbic System of the brain and intake (energy intake) is adjusted mainly
the maintenance of homeostatic conditions to the metabolic activity of the body (energy
in the body, it has concentrated its interest utilisation) which results in work and heat
Indian J Physiol Pharmacol 2001; 45(3) Fifty Years Following Discovery ofFeeding Centre 273
production. Therefore, it is essential that regarded as problems in the physiology of
the central nervous mechanisms that digestion. However, a large number of
regulate food intake should obtain precise experimental studies have brought out that
information about the other three variables, these are mostly dependent on the
which are also controlled through adjoining functional activity of the central nervous
areas in the central nervous system. system.
Information about both energy intake and
energy utilisation is provided to the Whereas early during the present
hypothalamic mechanisms related to century hunger was scheduled to have a
feeding. The hypothalamus also provides "peripheral" or gm, dependent upon
i
an important regulatory mechanism rhythmic gastric hunger contractions,
adjusting heat loss from the body to heat evidence gradually accumulated against this
production, the latter being further "peripheral" theory. For example, feeding
dependent on energy utilisation resulting persists even after the operation on the
III work. stomach, including nearly complete removal
of the organ. Similarly, denervation of the
It is thus apparent that the stomach in human subjects does not alter
hypothalamic mechanisms, which regulate the appetite.
food intake, play the most important role
in maintaining energy balance. Their
(a) Hypothalamic Mechanisms
activity is influenced through feedback of
information about energy utilisation, and is
Attention began to focus on the
further modulated through needs of the
hypothalamic region as a possible regulator
body for maintenance of body temperature.
of food intake when Hetherington and
Ranson in 1940 were able to induce obesity
If the regulatory mechanisms are able
in rats by bilateral hypothalamic lesions in
to integrate all of these activities, food
the region of the ventromedial nuclei. Later
intake will be precisely balanced with work
on other authors confirmed that such
done and heat produced, and so there will
obesity is due to "hyperphagia" (overeating)
not be either a surplus work and deficiency
and not due to any disturbance of
ofenergy for extra storage depletion ofbody
metabolism per se.
stores. Thus, body weight may be
maintained at constant levels over long
As detailed earlier, during Dr Anand's
period of time. Cowgil has nicely summed
stay at Yale University in 1951 in Brobeck's
up this situation by stating that under a
Laboratory, he demonstrated that, while
variety of circumstances, and on a variety
bilateral lesions in rats in the ventromedial
of diets, "animals eat for calories".
regions produced "hyperphagia", lesions in
(ii) Central Nervous Mechanisms Related to lateral hypothalamus lead to complete
Feeding 'aphagia' and death of the animal due to
starvation (12, 13). Further, he found that
Hunger, appetite and satiety phenomena medial hypothalamic lesions produced
associated with foodintake, were previously hyperphagia only when the LHA was intact.
274 Mallick Indian J Physiol Pharmacol 2001; 45(3)
If the lateral areas are bilaterally lesioned the hypothalamus that regulate food intake,
following medial lesions, hyperphagia is namely a mechanism in the lateral region
immediately changed to complete aphagia. ofthe hypothalamus which initiates feeding
If medial lesions follow lateral lesions, and is therefore designated as the "feeding
aphagia is still maintained. The lateral centre", and one in the medial part of the
hypothalamic area, bilateral destruction of .hypofhalamus which brings about satiety
which results in aphagia, is a discretely after a meal has been taken and is thus
located, well-defined, very small region, in termed the "satiety centre". The satiety
the same rostro-caudal plane as the centre is connected by lateral projections to
ventromedial nucleus. If this region is the feeding centre (21). The feeding centre
intact even on only one side complete has the basic hunger mechanism which
aphagia does not result. Lesions in any provides 'drive' to eat and thus results in
other region of the hypothalamus do not motivated feeding behaviour, and its activity
produce any quantitative changes in food is inhibited when the satiety centre is
intake. He also observed that lesions activated after a meal has been taken.
between the medial site and the lateral site
also result in hyperphagia, indicating lateral (b) Brain-stem Mechanisms
projections from medial area. Because these
results obtained in rats were later confirmed Feeding behaviour is based on feeding
in many other species of animals (14-18), reflexes operating through the spinal cord
they established the role of hypothalamus and brain stem levels. These reflexes are
in the regulation offoodintake. Stimulation activated by sensory stimuli that make the
of these hypothalamic regions in animal aware ofthe presence of food. These
unanaesthetised animals, through reflexes are facilitated by the feeding centre
chronically implanted electrodes, produces and inhibited from the satiety centre by way
effects on food intake, which are opposite of the projection of descending influences
to those produced by lesions (19,20). When from the hypothalamic centres onto the
stimulation of the LHA was initiated, the brain-stem mechanisms (22,29). Thus, when
animal would start eating immediately, the feeding centre is active it sends
irrespective of whether it had been fasted descending influences, which facilitate the
or previously fed. Similarly initiation of feeding reflexes. In this state ofhunger, the
stimulation of the medial area stopped animal starts eating when it becomes aware
eating even when the animals were hungry of the presence of food through various
and eating. These particular behavioural peripheral sensations. On the other hand,
changes lasted only during the period of when the satiety centre has been activated
stimulation. But if stimulation of the LHA (by mechanisms described below), it inhibits
was carried out for a longer period (about the feeding centre through lateral
one hour or so), then the total food intake projections and thus eliminates the
for that day remained higher (19, 20). hunger state. It also inhibits the feeding
reflexes. This produces the state of satiation
All these studies have provided evidence during which the animal will not eat
that there are two opposing mechanisms in even when it is aware of the presence of
Indian JPhysiol Pharmacol 2001; 45(3) Fifty Years Following Discovery ofFeeding Centre 275
food.In case the brain-stem mechanisms are extremely consonant with the subjective
separated from the hypothalamic and other state.
cerebral regulations, as in a decerebrate
animal, the feeding reflexes are still (iii)Regulation of Activities of Central Nervous
possible. When such animals are fed purring Mechanisms Related to Feeding (Signals for
is also noted, suggesting a state of satiation. the Regulating System).
Adjustment of food intake to energy
(c) Higher Cortical Mechanisms
expenditure is a hypothalamic function. As
a result of feeding, certain changes are
Although the hypothalamic mechanisms
produced in the body, which directly, or
provide the basic states of hunger and
indirectly, stimulate the activity of the
satiation, these are further modulated and
hypothalamic satiety centre (and possibly
influenced from the limbic system of the
also the higher cerebral regions). The
brain, which modifies food intake through
satiety centre, by suppressing the activity
a discriminative selective mechanism, that
of the feeding centre, brings about the state
is through a "discriminative appetite" (23-
of "satiation". Subsequently, when the food
27). Lesions of the limbic system produce
eaten is disposed of through conversion to
only small and temporary changes in the
heat, work, or some form of stored energy,
amount of food intake. On the other hand
activation of the satiety centre is removed
such lesions result in loss of animals power
and the feeding centre becomes more active,
to discriminate between edible and non-
thus leading again to the state of "hunger".
edible objects. Such monkeys will put
According to this concept, satiety is
anything edible or non-edible, into
regulated rather than hunger. This
their mouth. In fact monkeys which
conclusion is in keeping with the
are ordinarily vegetarian, can be fed
observation that, after destruction of the
on meat after such limbic lesions.
satiety centre, the rate of feeding in the
Conversely, stimulation of these
feeding period is not much affected, but the
areas produces "eating automatism"
animals no longer show normal satiety
without any quantitative change in food
periods. Moreover, the observed constancy
intake.
of body weight and energy reserves, inspite
of great variations in energy expenditure,
(d) Necortical regions shows that there are regulatory mechanisms
that adjust food intake to energy
Neocor.tical regions also modify the expenditure.
functional activities of these regulatory
mechanisms, by way ofhabit formations and This regulation can be subdivided
conditioning (14,28). This may explain why into two components working within
inspite of the hypothalamic centres biometrically defined limits. The first and
providing subjective states of hunger or possibly the most important is the short-
satiety, human beings, and animals with term regulation, the other, operating over
higher encephalisation can alter their a longer period, may correct the errors of
feeding behaviour in a manner not the short-term regulation.
276 Mallick
Indian J Physial Pharmacal 2001; 45(3)
SHORT TERM REGULATION the activity of a single neuron in the
hypothalamic centres was recorded through
Various suggestions have been put stereotaxically guided microelectrodes,
forward regarding the nature of the change, distension of the stomach was observed to
or changes, produced as a result of feeding, increase firing rate of satiety neurons and
which signal to the regulating system that simultaneously to inhibit the neuronal
further feeding should be stopped. The discharge from the feeding centre (31).
. principal mechanisms for short-term These results followed specifically by the
regulation include, first of all, nervous distension only ofthe stomach, as distension
afferents coming from the gastrointestinal of the adjoining peritoneal cavity with
tract, which provide information about the balloons did not produce this response.
acts of eating, swallowing, and the presence Information about distension ofthe stomach
offoodin the stomach and intestines. Later is passed on to the hypothalamic centres
on, changes in the internal environment, through gastric branches of vagus as
produced as a result of eating, provide stimulation of these neurons duplicated the
information about energy balance. Because hypothalamic effects of gastric distension.
considerable delay is involved before precise On the other hand, when the gastric
information is supplied through the latter branches of the vagus were cut, gastric
channel, sensory information from the distension no longer activated the satiety
alimentary tract plays a role as adjustment neurons. This effect is produced only
of feeding behaviour, till the changes through the activation of gastric branches
introduced in the milieu interiuer. of vagus and not through projections
through lower central nervous regions, as
this is still maintained even after cutting
(a) Signals During Intake of Meals
through the brain stem (decerebration).
There is some suggestive evidence that
a certain amount of motoring during the Normal gastric hunger contractions, on
passage of food through the oropharyngeal the other hand, do not produce any changes
region affect the satiety centre as in the electrical activity ofthe hypothalamic
demonstrated by electroencephalographic centres (32). But if the satiety centre is
recordings from these centres during the act activated by some other means, this leads
of swallowing (30). With the distension of to inhibition of the gastric hunger
stomach brought about by intake of contractions. This means that when the
food, direct activation of the satiety centre, stomach is empty and the satiety centre is
with a simultaneous inhibition of the not active, gastric hunger contractions
feeding centre, occurs. This was shown merely add 'objective' feeling of hunger to
experimentally by distending the stomach the 'subjective' feeling produced through
through inflation of intragastric baloons. activation of the feeding centre.
This resulted in a significant increase in
the electrical activity of the satiety centre, After food passes on from the stomach
recorded electroencephalographic ally into the intestine, further sensory
through implanted electrodes. Also, when information is provided for the activation
Indian J Physiol Pharmacol2001; 45(3) Fifty Years Following Discovery ofFeeding Centre 277
of satiety centre through the mesenteric result of shifts of water among the several
nerves as their stimulation evokes electrical compartments of the body.
potentials in the region ofthe satiety centre
(33, 34). The activation of mesenteric (ii) Glucostatic or glucosensitive mechanisms
afferents is possibly produced through
products of digestion present in the small Mayer in 1953 postulated that in the
intestine, as there is experimental evidence hypothalamus there are "glucoreceptors"
suggesting the presence of chemoreceptors sensitive to blood glucose in the measure
in the intestinal mucosa, which are sensitive that they can utilize it. Dr Anand's group
to products of digestion. This sensory conducted a large number of experimental
information bridges the time lag (i)between studies to test this hypothesis. These
the passage of food from the stomach into studies provided conclusive evidence for
intestine and its digestion there, and (ii) a direct relationship between the
changes in the milieu interieur result from
electrical activity of cells in the
absorption of products of digestion. hypothalamic satiety and feeding centres,
and the levels of glucose utilisation worked
(b) Between Meal Information to the
out from the arteriovenous glucose
Hypothalamic Feeding Centres
differences, thus firmly establishing the
mechanisms of "glucostatic" regulation.
Absorption of the 'products of digestion
Electroencephalographic activity recorded in
causes changes in the internal environment
unanaesthetized animals through depth
(milieu interiuer) which then provide
electrodes chronically implanted in these
specific information to the hypothalmic
centres, showed that the activity of satiety
feeding centres (35). The ingestion of even
centre was significantly and selectively
a single meal is accompanied by a number
affected by changes in the blood sugar level
of changes in the body, both chemical and
(37,39). In another set of experiments
thermal that alone or together may act as
where electroencephalographic activity of
signals to the nervous regulating
these regions was recorded in animals at
mechanisms. Available experimental
different intervals after normal feeding, it
evidences, however, suggest that such a
was shown that the activity of the satiety
regulation is mainly 'chemostatic' especially
and feeding centres changes in a reciprocal
'glucostatic', rather than 'thermostatic'.
manner depending upon the state of hunger
or satiety, and also that this activity
(i) Chemosensitive mechanisms related to
correlates with the arterio-venous glucose
feeding
differences (40).
The hypothalamic centres contain
sensitive neurons capable of responding to Electrical activity of single neurons in
chemical qualities (signals) of the hypothalamic satiety and feeding centres
circulating blood (36-38). Among the was also recorded before and after exposure
important signals proposed are availability to intravenous infusions of glucose, or
or utilisation of glucose, concentration of insulin, or combinations of both (41). In
amino acids and water concentration as a fasted animals the activity of satiety centre
278 Mallick Indian J Physiol Pharmacol 2001; 45(3)
neurons was slower than that obtained from the level of glucose utilisation (44), and not
feeding centre neurons. Frequency ofspikes the level of arterial blood glucose, which
recorded from satiety neurons increased and activates the hypothalamic centres. After
that of feeding centre neurons decreased administration of pharmacological
significantly after glucose was given preparations like cyproheptadine, which
intravenously. Spike activity was specific to increases appetite and causes a decrease in
the satiety and feeding centre neurons as A-V glucose differences (glucose utilisation)
.spike activity of neurons in adjoining the activity of the satiety area was again
hypothalamus and cerebral regions did not decreased and that offeeding area increased
show any change. The spike activity of (45). Studies with other pharmacological
hypothalamic centres was also more closely preparations, which depress appetite, such
related to the magnitude of arteriovenous as fenfluramine (46-47), and nialamide (48)
glucose differences (levels of glucose suggest that they actively increase glucose
utilisation in the body), rather than to the utilisation in the body. Recording from
levels of arterial blood glucose per se. It these centres further indicated that
was also interesting to observe that reserpine, rastinon and preludin, also
immediately after infusion ofinsulin,for the produced comparable results (49,50).
first few minutes the frequency of spikes of
the satiety neurons was increased before a Respiration studies were also conducted
decrease in their activities was registered. in Warburg manometers on tiny slices of
This was due to an initial increase in hypothalamus containing the satiety and
glucose utilisation produced by insulin feeding regions, obtained from hungry and
injection followed by hypoglycaemia and fed animals. In fed (satiated) states both
decrease in glucose utilisation. Unit glucose and oxygen uptake were higher in
activities recorded of these neurons in the satiety region than in the feeding
response to production of glucopenia, region, whereas conversely, during fasting
therefore, resulted in changes in frequencies (hungry) states both glucose and oxygen
opposite to this following glucose infusion uptake were higher in the feeding centre
(42). region (51).
The dependence of the activity of satiety Further it was reported that single unit
centre neurons on the levels of glucose recordings from the hypothalamic centres
utilisation in the body has been further after mid collicular transverse cuts through
confirmed by the experimental use of the brain stem (52), the changes in the unit
chemical preparations that influence glucose activities of the satiety and feeding centre
utilisation. For example, after the injection neurons in response to glucose and insulin
of 2-Deoxy-D-glucose (which decreases infusions still could be reproduced. This
glucose utilisation and simultaneously raises conclusively proves that changes in the level
blood glucose level to some extent) the firing of glucose utilisation act directly on nerve
rate of satiety neurons were decreased and cells of the brain and not though any
those of feeding neurons were increased chemosensitive mechanisms which may be
(43). This conclusively suggests that it is present at the periphery, say in the liver.