Rise In Blood Sugar Research Articles

SIGNIFICANCE OF RISE IN BLOOD SUGAR LEVEL AFTER INJECTION OF EPINEPHRINE IN MENTAL DISEASE

MEASUREMENT of the rise in the blood sugar level after the injections of epinephrine has been used for many years as a means of estimating glycogen stores in the body 1 ; it is believed that all of the glycogen which is broken down to glucose during the test is derived from the liver, for epinephrine does not influence the glycogen content of muscle in man. 2 Evidence is available indicating that an excess of adrenocortical hormones, which favor glycogen formation, is present in patients with mental disease, 3 and therefore it was considered desirable to study the rise in blood sugar after injection of epinephrine in treated and untreated patients with mental disease in order to extend the earlier observations of others 4 in this respect. MATERIAL AND METHODS Fifty-one untreated patients, ranging in age from 16 to 50 years, were studied shortly after admission; 33 were women. The diagnosis

Metabolic effects of ACTH upon preexisting diabetes mellitus.

THE production of a diabetic state in normal people by administration of ACTH has been demonstrated (1). In patients with diabetes mellitus administration of ACTH has been shown to result in a marked rise of blood sugar (2), and administration of cortisone has produced intensification of glycosuria and increased requirements for insulin (3, 4). An increase in excretion of ketone bodies occurs in patients with combined Addison's disease and diabetes mellitus when cortisone is given (5). A study of the metabolic effects of ACTH given over a prolonged period of time to a patient with diabetes mellitus has not been reported. Although important, such an experiment is not justifiable in a patient with uncomplicated diabetes mellitus because of the danger of permanent intensification of the diabetic state. Recently the opportunity arose to study a patient with diabetes mellitus of long standing, who received a twenty-two-daycourse of ACTH in the hope of arresting a progressive subacute myelogenous leukemia. The ...

Experiences with postoperative temperatures above 108 °F: Use of hypertonic glucoses

T HE occurrence of exceptionaIIy high temperature in the surgica1 patient is of sufficient frequency to warrant a review of our own reactions to the probIem and its management. In such instances death ensues mainIy as a direct resuIt of fever and not the underIying pathoIogic condition. That patients can survive temperatures over 108’F. with fuII recovery has been shown repeatedIy.1-5 Experimenta1 work shows that Iiving tissue does not become irreversibIy damaged until the temperature reaches I I$‘F.~ It is the purpose of this paper to point out that if we can tide these patients over the temperature crisis, they wiI1 have more time to combat their diseases and a certain number wouId survive who wiI1 otherwise be Iost. A review of the physioIogic changes and a IogicaI pIan of treatment is therefore presented. The genera1 picture in extreme hyperpyrexia is one of marked metaboIic aIteration. The basa1 metaboIic rate is often +so to + 75 in severe cases. Such a sudden increase in metaboIism puts a severe strain on the resources of the body which, as we shaI1 see, are aIready overtaxed.7-g Thus oxygen is in great demand but is suppIied with diffIcuIty, for it has been shown that the oxygen tension of arteria1 bIood is materiaIIy reduced in cases of high fever.10a11 The puIse rate is increased from five to ten beats per minute for each degree rise in temperature (Fahrenheit). Later it becomes so rapid that insufflcient cardiac output occurs. The bIood pressure first rises and Iater faIIs to shock IeveIs, indicating inabiIity to cope with the situation. The blood voIume is progressively diminished due to Ioss of water by the skin and Iungs, and Iater by the advent of shock.12-14 The bIood becomes concentrated. When tissue fluid loss into the bIoodstream exceeds 5 cc. per kg. per hour, periphera1 coIlapse ensues. Progressive dehydration together with the high metaboIic rate then increases the body temperature even more, constituting a deadIy cycIe. As fever increases, the ganglion ceIIs of the centra1 nervous system shrink,16 tota chIorides faII,16 the CO2 content of the bIood is Iowered, the Iactic acid content of the bIood is increased by 30 to 78 per cent above normaI,” base is mobiIized from the tissues to the bIood, the bIood sugar rises early then faIIs as supplies become depleted and the non-protein nitrogen rises. The inorganic phosphorus faIIs due to the greatIy increased rate of gIucose utiIization. The earIy rise in blood sugar is dependent upon the Iiver which is so stimuIated in high fever to reIease sugar that it often overshoots its mark. Hypersecretion of insuIin and epinephrine occurs.1s These changes favor glycogenoIysis to meet the demand for fue1, unti1 the Iiver is depIeted of its gIycogen and disaster is at hand. Autopsy at this time reveaIs a marked decrease in Iiver gIycogen. In addition Iiver function becomes deficient as a resuIt of hyperpyrexia per se.1v--22 This is unfortunate inasmuch as the demands made upon the Iiver at this time demand a very efficient response. Thus jaundice, hepatomegaIy and Iiver faiIure have been noted foIIowing therapeutic hyperpyrexia.1g-21 The serum aIbumin and fibrinogen IeveIs faI1, again due to impaired Iiver function. AS a resuIt of insuffIcient avaiIabIe gIucose, proteins and fats are burned with remarkabIe rapidity to suppIy fueI.23-27 Thus incompIete fat combustion occurs and ketonuria is observed. Protein metaboIism is so aItered that more than 25 gm. may be burned per hour. GIucose may thus be considered as a protein and fat sparer. WhiIe these changes are taking pIace, the cardiopuImonary circuit is Iaboring desper-

THE EFFECT OF HYPNOTICS ON BLOOD SUGAR AND ON THE ACTION OF INSULIN1

The effect of barbiturates or morphine upon the blood sugar level has been the subject of several investigations but an examination of the results reported does not lead to convincing conclusions as will be evident from the following brief resume. Barbital sodium, as reported by Ellis and Barlow (1924), lowered the blood sugar in both cats and pigeons. Weiss (1926) has reported that barbital caused a marked initial rise in blood sugar in the cat and dog which is followed by a gradual fall. Jackson (1931) reported that in rabbits, barbital sodium retards the hypoglycemia produced by insulin. Murphy and Young (1932) have reported that pentobarbital and other barbiturates produced an increase in blood sugar in cats. Jarman and Abel (1933) reported that evipal sodium in humans produced no alteration in blood sugar. Hemingway et al. (1934) found that pentobarbital in the dog caused a slight increase in blood sugar.

The effect of adrenaline on the utilization of glucose

1. 1. This work was undertaken with the object of investigating whether the rise in blood sugar after adrenaline may at least be partly due to inhibition of glucose uptake by the tissue: more explicitly whether the hexokinase reaction determining the rate of glucose uptake by the tissues from the blood was impaired directly or indirectly after injection of adrenaline. 2. 2. There is a marked inhibition of the anaerobic glycolysis of diaphragms from rats which have been injected with adrenaline (1 mg/kg subcutaneously) 40–70 minutes previously. This inhibition is approximately 30–36%. The manometric result could be confirmed by chemical lactic acid estimations. The inhibition does not occur in the blank estimations in the absence of glucose. 3. 3. When various phosphate fractions like inorganic P (incl. creatine P), 7 min P, 15 min P, 180 min P and Total P were determined in diaphragms from adrenaline injected rats and compared with normal controls, no significant differences could be demonstrated. 4. 4. There is no essential difference in initial glycogen level between the diaphragms of treated animals and controls. The presence of glucose during anaerobic incubation seems to inhibit glycogenolysis in diaphragm from normal animals. It appears that quantitative differences in intrinsic substrate (glycogen, phosphorylated carbohydrate) cannot be responsible for the marked inhibition observed in the glycolysis of diaphragms from adrenaline treated animals compared with the controls in the presence of glucose. This inhibition only affects the metabolism of added glucose. 5. 5. When hexose diphosphate is used as a substrate no inhibition of the anaerobic glycolysis of diaphragm from adrenaline treated animals is observed suggesting the inhibiting action towards glucose to occur prior to the zymohexase reaction in the glycolysis chain. 6. 6. A direct inhibition of glucose utilization of diaphragm under influence of adrenaline added in vitro, cannot be demonstrated.

Hypoglycemic Action of Sulfanilamido-cyclopropylthiazole in Rabbits, and Its Reversal by Alloxan

Summary1. 2-Sulfanilamido-5-cyclopropyl-1,3,4-thiadiazole, like other sulfonamides, has a chemotherapeutic action against certain pathogenic bacteria. It has a low toxicity. There is no evidence of conjugation as. judged by blood examination.2. When given to normal rabbits, the substance uniformly causes hypoglycemia-with or without a slight initial rise of blood sugar. On the other hand, in diabetic rabbits induced by alloxan, it produces a definite rise of blood sugar.

CARBOHYDRATE METABOLISM AFTER BURNING

1. Burning caused a rise in the blood sugar of both rats and rabbits anæsthetised with ether. In rabbits, this rise was greater in well‐fed animals than in those starved for 24 hours, and had completely disappeared 24 hours after burning. In both species, adrenaline injections produced a similar hyperglycæmia. In rats, whose adrenals had been removed, there was no rise in blood sugar after burning.2. Rats had a higher blood lactic acid one hour, but not 3 hours, after burning; adrenaline injections produced similar changes in blood lactic acid.3. Both one and 3 hours after burning, there was a fall in the glycogen content of the whole carcass (chiefly muscle glycogen) of rats. Similar changes were observed after adrenaline injections. The carcass glycogen of burned adrenalectomised animals remained normal.4. Rabbits deprived of food for 24 hours and burned, had a lower liver glycogen, both 4 and 24 hours after burning, than the controls, which had been merely anæsthetised. On the other hand, burning produced no change in the liver glycogen of either normal or adrenal‐ectomised rats starved for 24 hours, but the injection of adrenaline caused a slight rise.5. Liver slices from rabbits killed 4 hours after burning formed glycogen from glucose less readily than slices from anæsthetised control animals. Slices from similar animals, killed 2‐4 hours after an injection of adrenaline which produced a similar degree of hyperglycæmia, formed glycogen normally.6. Liver brei from burned rabbits did not break down glycogen, either by phosphorylase or amylase activity, any more rapidly than a similar brei from control animals.7. There was no increase in the amylase activity of serum of rabbits either 4 or 24 hours after burning.8. There was a fall in the ascorbic acid content of the adrenal gland of rabbits, both 4 and 24 hours after burning, but no change in the ascorbic acid of the liver.9. Injection of 5 ml. of isotonic ammonium chloride intraperitoneally into rats caused a rise in blood sugar of the same order as that observed after burning, but the plasma alkali reserve, after such an injection, was much less than that observed after burning. Intraperitoneal injection of 5 ml. of isotonic sodium bicarbonate did not influence the burn hyperglycæmia any more than a similar injection of 5 ml. isotonic sodium chloride. It is concluded that acidosis plays no part in burn hyperglycæmia.10. Well‐fed rats were no better able to survive burning than similar animals starved for 24 hours.11. The mechanism of burn hyperglycæmia is discussed. It is concluded that there are at least two distinct processes at work:(a) the liberation of adrenaline from the adrenal glands;(b) some other process or processes, either stimulating hepatic glycogenolysis or inhibiting glycogenesis.12. The source of the glucose is chiefly the muscle glycogen, and it is suggested that it is mobilised by a mechanisnm similar to the Cori cycle.13. As a practical measure, it is suggested that during the period of shock and hæmoconcentration burn patients should be given diets rich in carbohydrate.The authors wish to thank Professor R. A. Peters, F.R.S., for his continued interest in this work. Thanks are due to Miss J. Jenkins for valuable technical assistance. One of us (E. J. C.) is indebted to the Medical Research Council and one (R. J. R.) to the Carnegie Trustees for a personal grant. The Medical Research Council has also contributed towards the cost of this investigation.

Blood Lactic Acid in Liver Glycogen Disease

An Increase in the amount of circulating lactic acid is generally attributed to anoxia. This is the cause of the high values obtained during muscular work, in cardiac decompensation, anemia, pneumonia, and shock. The concentration of lactic acid in the blood can, however, be raised above the normal fasting level by the injection of epinephrine. Cori has demonstrated that in this case the lactic acid comes largely from the breakdown of muscle glycogen. This phenomenon is apparently not associated with anoxia. We have recently had the opportunity to observe 2 infants with a singular disease, in which the high blood lactic acid would seem to be due to some other mechanism than that postulated. The disease in question, commonly known as hepatic glycogen disease or von Gierke's disease, is characterized by a defect in liver metabolism, in consequence of which the liver accumulates abnormally large stores of glycogen which it is unable to transform into glucose and excrete into the blood as a normal liver does during hypoglycemia. The patients are female infants; one 6 months, the other 61/2 months old. Both have very large livers. Neither shows any rise in blood sugar after the injection of epinephrine. Both tend to have very low blood sugar if not fed more frequently than a normal infant. Both have had convulsions due to hypoglycemia. Simultaneous determinations of blood sugar and lactic acid have been made 110 times. An analysis of the correlation of these individual determinations shows no consistent relation between the height of the blood sugar and that of the lactic acid. When, however, these infants are fed soy bean mixture and corn syrup at the usual 4-hourly intervals and also given 30 to 50 cc of a 10% glucose solution every hour between feedings, the blood sugar stays at normal or slightly higher levels and the lactic acid remains at between 20 and 50 mg per 100 cc (Fig. 1).

Blood Sugar and the Follicles of Langerhans in the Ammocoete Larva

ABSTRACT Glandular follicles, first described by Langerhans, develop in the wall of the alimentary canal of the ammocoete larva at the point of junction of fore- and midgut, and have often been compared with the pancreas of higher forms. They have been re-examined histologically, using Helly’s fixative and the ‘Azan’ stain, and the view of some recent workers, that they have the appearance of endocrine structures, is confirmed. They comprise only one type of cell, however, which shows no decisive resemblance in staining reaction to any of the cell types characteristic of typical islet tissue. The injection of glucose into ammocoetes usually produces a marked response in these cells, involving extensive vacuolization, while destruction of the follicles by cautery induces a significant rise in blood sugar. These reactions, which imply that the follicles are involved in carbohydrate metabolism, are similar to those associated with the B cells of islet tissue. It is concluded that the evidence, while not yet complete, suggests that the follicles represent a primitive stage in the evolution of the endocrine component of the vertebrate pancreas, and it is pointed out that ‘follicles of Langerhans ‘would be an apt designation for them. Further work will be necessary to Clarify their relationship to the islets of Langerhans of higher forms.

Observations in Hypoglycaemia. II. Blood Sugar and Consciousness

Since Sakel's introduction of hypoglycaemia into the therapy of psychoses, discrepancies between the level of the patient's blood sugar and the severity of disturbance of consciousness have frequently been noted. The blood sugar decreases in a relatively steep curve within the first and second hour after the injection of insulin; but only after it has remained on a low level—differing from case to case—for a considerable time does the patient go into coma.It seems useful to define the clinical signs of coma if it is intended to correlate it with laboratory findings. It is a state of unconsciousness in which the patient cannot be roused by sensory stimuli; in coma such stimuli do not provoke local and purposeful, but global movements only, if any. Once in coma the patient remains so, independently of the blood-sugar level, which can rise and fall within a certain range without visible change in the clinical picture; it may even rise to a level at which the patient was awake or could be easily wakened before he went into coma. Subcutaneous or intravenous injections of adrenalin in coma produce a rise in blood sugar without clinical effect. On the other hand, the flooding of the blood stream with sugar by nasal tube feed of a concentrated sugar solution or by intravenous injection of 33 per cent. glucose solution terminates coma and restores consciousness within a few minutes. The latter's action is so immediate that it is considered a practical rule not to stop injecting glucose until the patient is really awake.From these observations coma appears to be a kind of trigger mechanism comparable to instinctive reactions, such as thirst, hunger or sexual desire. Once established it can only be reversed by specific means.

PHYSIOLOGICAL AND PHARMACOLOGICAL INVESTIGATIONS ON THE NATURE OF HYPOTHALAMIC EXCITATION

1. Experiments are briefly cited in which in narcotized cats, the hypothalamus was stimulated and the contraction of the nictitating membrane on the same side recorded. In addition to this the cephalad end of the cervical sympathetic was stimulated on the contralateral side, and the contractions of the corresponding nictitating membrane were recorded also. This preparation allows one to distinguish between central and peripheral effects. It was shown that anoxia, inhalation of excess carbon dioxide and various convulsant drugs, such as metrazol, coramine, picrotoxin and coriamyrtin, increase the excitability of sympathetic hypothalamic centers on intravenous injection. The most effective drug is metrazol, which may produce signs of increased sympathetic discharges as measured by the height of the contraction of the nictitating membrane for long periods of time. 2. The effects of anoxia and of metrazol convulsions were investigated on normal rats and animals in which the adrenals had been removed. Furthermore, rats were used in which, in addition to the removal of the adrenals, the vagi had been divided below the diaphragm. It was found that anoxia and metrazol, while producing a hyperglycemia in the normal animal, lower the blood sugar level in the adrenalectomized rat. If, however, the vagi are divided in adrenalectomized animals, anoxia and metrazol no longer produce a hypoglycemia, but call forth merely a slight and delayed rise in blood sugar. The experiments are interpretated to mean that anoxia and metrazol produce a simultaneous excitation of the sympathetico-adrenal and vago-insulin system in the normal animal, but that the excitation of the latter does not become apparent on account of the predominance of the sympatheticoadrenal system. 3. It is shown that electrical excitation of the hypothalamus leading to a typical rage response produces a rise in the blood sugar in the normal, but a fall in blood sugar in animals with adrenals eliminated and liver denervated. If, however, the vagi are cut, the hypoglycemic effect disappears and a delayed slight hyperglycemia (due to sympathin?) occurs. It is inferred that the process of sham rage is characterized by a simultaneous discharge over both divisions of the autonomic nervous system. 4. If cats in which the spinal cord had been divided at the sixth cervical segment, in order to eliminate excitation of the sympathetico-adrenal system, are exposed to a barking dog they react with reversible hypoglycemia. This reaction is absent when the vagi are cut below the diaphragm. It is inferred that emotion involves both vagal and sympathetic excitation. The former leads to increased secretion of insulin, the latter enhances the secretion of adrenalin.

The Autonomic Basis of Emotion

(1) It is shown that hypothalamic stimulation in cats, with faradic currents eliciting the syndrome of sham rage, produces after the elimination of the sympathetico-adrenal system a hypoglycemia when the vagi are intact. After bilateral vagotomy the stimulation results in a slight and delayed rise in blood sugar. (2) If in cats in which, due to a sectioning of the spinal cord at the sixth cervical segment, the effect of central discharges on the sympathetico-adrenal system is eliminated, a rage response is elicited by a barking dog it produces a fall in blood sugar. The sectioning of the vagi below the diaphragm abolishes this reaction. From these experiments it is concluded that the normal emotional process as well as the sham rage reaction is characterized by a simultaneous discharge over the vago-insulin and sympathetico-adrenal system. The latter predominates in the normal animal and masks the effects on the former.

The Effect of Eimeria tenella (Coccidia) upon the Blood Sugar of the Chicken

During the course of preliminary experiments it was discovered that the amount of blood sugar in the chicken increased during cecal coccidiosis. The following experiments are directed toward the problems involved in carbohydrate metabolism in the chicken, both normal and during the acute stages of a coccidiosis infection in an effort to learn something about the extent, duration and possible causes for the rise in blood sugar. The blood sugar of normal chickens has been studied by a number of investigators. This work has been summarized by Shimer (1937). The average blood sugar found in the chicken by eleven different groups of workers varied from 139.1 milligrams per 100 cubic centimeters of whole blood to 259.4 mgms. The mean value for these averages falls between 170-180 mgms. Shimer's own experiments gave an average figure of 192.25 mgms. when 90 birds were tested.

THE EFFECT OF PONTINE TRANSECTION ON THE BLOOD‐SUGAR LEVEL OF THE DECEREBRATED FASTING CAT

Mid‐brain decerebration in the fasting cat resulted, an hour later, in an average blood sugar of 220 mg. per cent., tending to rise to about 250 mg. in 3 hours' time, thereafter falling slowly. When decerebration was through the pons, the level was at first some 30 mg. higher, and in 4 hours rose to almost 340 mg.The initial high sugar consequent on mid‐brain decerebration was not maintained in absence of the adrenals (removed just after decerebration).“Bleeding back” behind the tentorium disturbed markedly both respiration and blood‐sugar concentration, preventing the usual fall of the latter.Destruction of the pituitary, immediately after decerebration, did not make the rate of change of blood sugar any different from that in animals where it was left in situ (though cut off from the brain stem).Cutting, at the start of the experiment, all the structures at the liver hilum, save the portal vein, did not alter the usual behaviour of the blood sugar of the decerebrate animal. Cutting at a later stage was followed by a slight rise in blood pressure, and an average rise of 50 mg. in blood sugar, apparent even in the adrenalectomised animal.High concentrations of liver glycogen did occur 3 hours after decerebration but the average value was 1–3 per cent. Decerebrate animals with high liver glycogen at this stage usually had a high initial, slowly falling blood sugar.Pontine transection some time after decerebration was followed by an average rise in blood sugar of 70 mg. A perceptible, though very small, rise in sugar occurred in absence of adrenals or of hepatic nerves (the latter were cut about 3 hours after decerebration). If the nerves had been out immediately after decerebration the rise in sugar following transection was just as great as when both adrenals and nerves were intact. In absence of adrenals and hepatic nerves, transection of the pons did not interrupt the trend of blood sugar evidenced prior to the section.The main cause of the blood‐sugar rise following transection of the pons of the fasting decerebrate animal is certainly liberation of adrenaline from the suprarenals.A considerable rise in blood pressure followed pontine transection even in the adrenalectomised decerebrate animal.Destroying the hepatic nerves by tearing and application of phenol left an appreciably higher liver glycogen content than when all the hilum structures save the portal vein were cut, suggesting that the arterial flow to the liver may be of consequence in this connection.The author acknowledges with thanks his indebtedness to the Medical Research Council for a grant in aid of expenses; to Professor Brocklehurst for facilities in the Department of Physiology, University of Bristol, where part of the investigation was carried out; to the late Professor J. J. R. Macleod, and to Professor A. Hemingway and Dr. J. M. Peterson for their interest and encouragement.

EFFECT OF SYMPATHIN ON BLOOD SUGAR

Cannon and Rosenblueth (1933,1935) have shown that sympathin, although like adrenine in action, is not identical with it. It seemed desirable to see whether it affects carbohydrate metabolism as adrenine does. Bacq (1933), indeed, observed a slight rise in blood sugar in two animals after stimulation of the lower abdominal sympathetic chains. But the small number of Bacq’s experiments and the fact that Cannon and Rosenblueth (1933) by stimulating either the cardio-accelerator or the liver nerves obtained much more sympathin than was possible with Bacq’s technique suggested a study of the effect of sympathin on blood sugar in a larger number of animals and with more favorable conditions. Of the two rich sources of sympathin mentioned above, we had to use the cardio-accelerator nerves since, obviously, stimulation of the liver nerves would cause marked changes in the hepatic blood supply. METHODS. Cats were used in this investigation. In order to stimulate the cardio-accelerator nerves without disturbing the blood-sugar level by involvement of the liver and the adrenal glands in an acute experiment, the adrenal glands had to be inactivated and the sympathetic innervation of the liver had to be destroyed in preliminary operations. This was done usually about two weeks before the actual experiment. The right adrenal was removed; the left was denervated by severing the left splanchnic nerves, excising that portion of the coeliac plexus in which they terminate, and removing the upper part of the left lumbar sympathetic chain (ganglia I, II and III). Also the left adrenal gland was demedullated by curettage after the medulla had been exposed through a lateral incision in the cortex. Sometimes the left adrenal was first denervated and demedullated and in a second operation the right adrenal was removed. The destruction of the sympathetic innervation of the liver was carried out either by partial removal of the right sympathetic chain (from Th VII to L IV) in addition to the above operation on the left chain, or by severing the nerves in the hepatic pedicle and then painting it with con-

Dinitrophenol Hyperglycemia. II. Its Prevention by Section of Splanchnic Nerves.

In a study of the hyperglycemia produced by 2–4 dinitrophenol (DNP), Hall, Brown and Sahyun1 suggested that its mechanism might be the stimulation of sympathetic glycogenolytic centers of the brain stem by local cellular anoxemia or acidosis. Wishnovsky, Kane, Schlevin and Byron2 have criticized this suggestion, on the grounds that the rise in blood sugar produced by the drug may still be demonstrated after the administration of large quantities of glucose, at a time when, as they state “the tissues are flooded with dextrose and the predominant process in the liver is glycogenesis. There is no need for active glycogenolysis.” They were at a loss to explain the observed rise.In order to determine whether DNP hyperglycemia depends upon impulses arising in the central nervous system and causing hepatic glycogenolysis, we have cut the 3 splanchnic nerves of cats just below the diaphragm on both sides under aseptic conditions. Controls were subjected to the same procedure except that the nerves were not actual...

Some Observations Upon Blood Glucose in Epilepsy

Pigott has recently reported low blood sugar in epileptic convulsions and regards hypoglycemia as a possible etiological factor. In our series of 25 cases in which 3 or more determinations have been made in each case we do not confirm this view. The blood glucose was determined by the method of Gibson. Determinations were made before, during and after seizures and in each case the blood glucose was within normal limits (90 to 110 mg. per 100 cc. blood) before convulsions, and rose during the convulsions. The rise of blood sugar was roughly proportional to the severity of the seizure, and after termination of the convulsion the blood sugar returned to normal in two to four hours. In 4 cases of status epilepticus the blood sugar value before seizure was 95.0 to 100.0 mg. per 100 cc. blood. After about one hour of status the values rose to 139.0 to 190 mg. per 100 cc. and after three hours of status the values were 150 to 240 mg. per 100 cc. In 21 cases having moderate to very severe isolated seizures the blood sugar rose from the average of 92.5 mg. per 100 cc. blood before seizures to 168.0 mg. per 100 cc. during convulsions. In 7 cases the elevation of blood sugar was above 185 mg. per 100 cc. during the height of the convulsions.

Effect of Epinephrin on Normal and Diabetic Response to Insulin

The search for a cause of the marked difference in the course of action of insulin intravenously injected in the normal and depancreatized dog brings up the question whether epinephrin secretion in response to low blood sugar can be responsible for the rapid return to the initial level which sets in at 20 to 25 minutes in the normal animal. When the action of 3 mg. of epinephrin (3 cc. of 1:1000 solution) is superimposed on insulin action in normal and diabetic dogs they still show respectively a curve with a definite minimum at 20 minutes and a continuous drop to at least 60 minutes. Eight experiments were carried out to cover a reasonable dose range of both drugs. An example is given in Table I. According to the data of Hrubetz the amount of epinephrin given should be more than enough to counteract the insulin effect if the 2 drugs were direct antagonists. Control experiments where epinephrin alone is given, as well as the late blood sugar rise when both drugs are given, indicate also that the epinephrin dose is large enough to meet the requirements of the experiment, i. e., give a blood sugar raising effect equal to the blood sugar lowering effect of the insulin. Against a background of several hundred blood sugar curves we would judge that with the doses here used the epinephrin has little effect on the course of insulin action and asserts itself only after the action of the latter has passed off. The lack of rapid return of blood sugar towards the initial level in the diabetic animal cannot be attributed to absence of mobilizable liver glycogen. Epinephrin alone causes the usual mobilization of sugar in the diabetic dog.

CORTICOADRENAL INFLUENCE ON BLOOD SUGAR MOBILIZATION

The adrenal gland, and more particularly the adrenal medulla, has long been associated with variations in blood sugar. Papers on the effects of adrenin (epinephrine) in physiological and pharmacological amounts comprise a voluminous literature that is constantly increasing. We shall not attempt to discuss it in this paper. In general it is now accepted that increased activity of the adrenal medulla or injections of its active principle result in a rise in blood sugar. Conversely, the low blood sugars found in patients suffering from Addison’s disease or in completely adrenalectomized animals have been frequently attributed to loss of the medulla and its adrenin. We do not agree with the latter view, since it has been shown that dogs (Houssay and Lewis, 1923) and cats (Zwemer, 1924, 1927) having the cortex only of one adrenal survive normally for some time. Furthermore, determinations made on animals so prepared showed that the loss of the adrenal medulla does not greatly affect the blood sugar level of surviving animals. Wyman and Walker (1929) have reported the relation of the adrenal cortex to blood sugar in the rat. Recent emphasis by Britton and Silvette (see bibliography) on the extreme importance of carbohydrate metabolism in adrenal cortex physiology led us to gather together our data* on this subject.

Ether Hyperglycemia

Glycosuria following etherization was first observed by Reynoso, while the increase of blood sugar accompanying ether anesthesia was first reported by Seelig. Section of the nerves to the liver does not prevent the hyperglycemia resulting from the administration of ether. If the adrenals are inactivated, however, this rise in blood sugar is in large part prevented, as Keeton and Ross showed. That adrenin rather than the action of sympathetic impulses is the potent factor in liberating sugar from the liver has been shown by Bulatao and Cannon and by Britton. Reid had advanced evidence that the hyperglycemia resulting from etherization is due to secretion of adrenin. But after removal of the adrenal factor ether still produces an increase of blood sugar. The demonstration by Cannon and Bacq, that stimulation of the sympathetic nerves produces sympathin and that sympathin resembles adrenin in action, suggested that the residual hyperglycemia from etherization after adrenal influence had been excluded might result from the action of sympathin. If this idea were correct the level of blood sugar should not rise when ether is administered to completely sympa-thectomized animals. Healthy adult cats were maintained in good condition on an adequate diet and fasted for 24 hours before the experiment. Blood (0.1 cc.) was drawn from an ear vein for sugar determinations, which were made in duplicate by the Folin-Svedberg method. The sugar level was determined before etherization and every 15 minutes thereafter, during the administration of the ether, for one hour. A final analysis was made one hour after cessation of the anesthesia. The ether was administered carefully in order to avoid struggle and to minimize emotional reactions. As soon as relaxation was obtained a tube was inserted between the vocal cords into the trachea, and artificial respiration was started in order to avoid asphyxia. The depth of the anesthesia was regulated so that the corneal reflex was just present. Experiments were performed on normal cats, on cats with the left adrenal denervated, the right removed and the hepatic nerves cut, and on cats completely sympathec-tomized. The completeness of the sympathectomy was assured by noting absence of erection of the hairs on exposure to cold or during emotional excitement. Careful necropsy verified these findings. Summary. The elevation of the blood-sugar level in cats on etherization (Fig. 1A) is considerably reduced by inactivating the adrenals and cutting the liver nerves (Fig. 1B). The residual increase persists in the completely sympathectomized animal (Fig. 1C), and therefore does not result from the production of sympathin. The persistent hyperglycemia does not depend upon direct stimulation of adrenal secretion by ether since it is still present when both adrenals have been removed in the completely sympathectomized cat (Fig. 1E).