Hypoglycemic Convulsions Research Articles

USE OF GLOBIN INSULIN IN ADDISON'S DISEASE ASSOCIATED WITH INSULIN-SENSITIVE DIABETES

IN 16 cases of coexisting diabetes mellitus and Addison's disease so far reported in the literature, insulin sensitivity has been a frequent occurrence and has presented a difficult therapeutic problem. In three of the cases reported, diabetes developed after the onset of Addison's disease (1, 2, 3). Simpson's (1) patient had been treated elsewhere with epinephrin injections. Following treatment with adrenal cortical extract, hyperglycemia and glycosuria developed within one month. Insulin was administered. This resulted in severe hypoglycemic reactions from even small doses. The patient eventually came to autopsy and the diagnosis of Addison's disease was substantiated. The patient described by Rhind and Wilson (3) was treated with desoxycorticosterone for one year and then developed diabetes. This individual was the only one of fifteen who was apparently not extremely sensitive to insulin. The patient was taking 60 units of insulin per day and eventually expired in a hypoglycemic convulsion.

Relation of Adrenal Gland and Hypophysis to Blood Sugar Levels Following Administration of Alloxan.

SummaryAn initial hyperglycemia did not appear in either adrenalectomized or hypophysectomized rats injected with alloxan. with the doses of alloxan used, hypoglycemic convulsions did not appear in any of 15 intact animals whereas convulsions occurred within 6 hr in all of 14 adrenalectomized and 9 of 10 hypophysectomized animals. In the absence of the adrenal medulla the reaction to alloxan was the same as in intact animals; removal of the adrenal cortex (regenerated cortex following adrenal enucleation) resulted in the same reaction as total adrenalectomy.

Influence of Metrazol, Insulin Hypoglycemia, and Electrically Induced Convulsions on Reestablishment of Inhibited Conditioned Reflexes

In a series of studies it was shown that convulsions induced by metrazol and other convulsant agents or by electroshock as well as insulin hypoglycemia are accompanied by an increased excitability of autonomic centers at the hypothalamic and medullary level.1 It was thought that this action is of greatest importance for the shock therapy of psychoses and may explain the fact that these procedures have similar therapeutic effects although their action on the cortex as measured by the electroencephalogram is quite dissimilar.2It seemed probable that hypoglycemic coma and convulsions may have in addition to their temporary influence on the cortex as revealed by the electroencephalogram far reaching effects on cortical processes which would be detected best by chronic experiments. Therefore the effects of these procedures on the conditioning process were studied.The experiments were performed on 17 rats which received as an unconditioned stimulus a shock inducing them to jump from a compartment A across a sma...

ASSAY OF INSULIN ON HYPOPHYSECTOMIZED, ADRENO-DEMEDULLATED, AND HYPOPHYSE-TOMIZED-ADRENO-DEMEDULLATED RATS1

Journal Article ASSAY OF INSULIN ON HYPOPHYSECTOMIZED, ADRENO-DEMEDULLATED, AND HYPOPHYSE-TOMIZED-ADRENO-DEMEDULLATED RATS Get access E. GELLHORN, E. GELLHORN 1From the Departments of Physiology and Psychiatry, University of Illinois, College of Medicine CHICAGO, ILLINOIS Search for other works by this author on: Oxford Academic Google Scholar J. FELDMAN, J. FELDMAN 1From the Departments of Physiology and Psychiatry, University of Illinois, College of Medicine CHICAGO, ILLINOIS Search for other works by this author on: Oxford Academic Google Scholar A. ALLEN A. ALLEN 1From the Departments of Physiology and Psychiatry, University of Illinois, College of Medicine CHICAGO, ILLINOIS Search for other works by this author on: Oxford Academic Google Scholar Endocrinology, Volume 29, Issue 1, 1 July 1941, Pages 137–140, https://doi.org/10.1210/endo-29-1-137 Published: 01 July 1941 Article history Received: 13 March 1941 Published: 01 July 1941

Influence of Emotional Excitement on Insulin Content of Blood in Normals and Psychotic Patients

It was shown recently that emotional excitement leads to a discharge over both vago-insulin and sympathetico-adrenal systems, the effect on the latter predominating in the normal animal. These observations are supplemented by the present studies in which the insulin concentration of the human blood was determined by an assay on the hypophysectomized-adreno-demedullated rat. If 1 cc of normal human blood is injected intraperitoneally into such rats and the blood sugar is determined after one hour a very slight fall in blood sugar is observed and the animals do not show any symptoms (A). If, however, excited psychotic patients are tested it is found that their blood produces a marked hypoglycemia in test animals, frequently leading to coma or hypoglycemic convulsions. It is noteworthy that this result was regularly obtained with the blood of 13 excited patients (C, Table I) whose blood sugar was unaltered. Moreover, in 2 cases (G) it could be shown that in quiet periods following the excitatory state the test no longer indicated increased amounts of insulin in the blood but produced a reaction similar to that of our control cases. Apparently emotional excitement leads in these cases predominantly to an increased secretion of insulin, whereas in normals the effect on the sympathetico-adrenal system prevails., This conclusion is supported by the comparative study of Groups B, C, and D. Students excited by the writing of the semester examination served as controls. Their blood sugar was somewhat elevated and caused a slight rise in the blood sugar of the test rat (B). The blood of an excited patient with a similar hyperglycemia (D) caused a conspicuous hypoglycemia in the test animal. Even in the case of Group E in which emotional excitement led to a more marked hyperglycemia indicating a much greater adrenalin secretion than in the excited controls (B), the test animal reacted with a slight hypoglycemia similar to that found in the unexcited control group. Obviously, the insulin concentration of the blood was increased sufficiently to offset completely the effects of adrenalin on the blood sugar of the test animal.

Sugar Utilization in Hypophysectomized Rabbits

The fact that serious hypoglycemia may develop in hypophysectomized rabbits and dogs is well known. In preliminary experiments it was found that glucose must be administered to fasted hypophysectomized rabbits to prevent hypoglycemic convulsions and death. The animal requires large amounts of sugar even when the blood sugar level is low. The work reported here was concerned with the measurement of this requirement. The aim was to determine the minimum amount of glucose necessary to maintain a proper blood sugar level in fasted hypophysectomized rabbits. After a 3-day fast the pituitary was removed by an oral approach (Cope's) modification of White's method. Frequent blood sugar estimations were carried out after the hypophysectomy. When the level had fallen to 80 mg. % or lower sufficient 10% glucose was given intravenously every hour thereafter to keep it from going lower. The rate of injection was adjusted according to whether the previous blood sugar had indicated the level was rising or falling. The interval between time of operation and time when the blood sugar began to drop varied in different rabbits from 11 to 32 hours. The amount of glucose required increased during the first 5 to 8 hours thereafter, by which time a maximum requirement was attained. There was little increase above this. Glucose was given in some cases by continuous intravenous injection. In a given animal, the amount required was the same whether the glucose was given at one hour intervals or by continuous injection. Urinary determinations for sugar were uniformly negative. The amounts of glucose which had to be injected during the period of maximum need is recorded in grams per kilo body weight per hour in Table I.

Hypophysectomy of birds II—General effects of hypophysectomy of fowls

It was originally supposed, mainly as the result of experiments on dogs, that the presence of the pituitary body was essential to life (see Cushing (1912) for discussion and references). Recent work, however, has shown that, in many species, the removal of the pituitary is not fatal. Thus dogs (Houssay (1932) and Houssay and Biasotti (1931) ), cats (Allan and Wiles (1932)), and rabbits (Smith and White (1931) ) show a fair survival rate, and rats (Smith (1930), Collip, Selye, and Thompson (1933)), and ferrets (Hill, M., and Parkes (1932)) a high survival rate after complete removal of the pituitary. Apart from regressive changes in the other endocrine organs, the most serious consequence of hypophysectomy appears to be disturbance of the carbohydrate metabolism. This dis­turbance varies in severity in different species, but in some it is responsible for at least a proportion of the deaths following hypophysectomy. Thus Houssay (1932) and Houssay and Biasotti (1931) consider that the anterior lobe of the pituitary is responsible for the formation of new carbo­hydrate from endogenous protein and that in the absence of the pituitary an animal is entirely dependent on pre-formed carbohydrate. This supposition is in keeping with the fact that hypophysectomized dogs occasionally develop a spontaneous fatal hypoglycaemia, while White (1933) observed that fatal hypoglycaemic convulsions were not uncommon among hypophysectomized rabbits. The spontaneous hypoglycaemia which may occur in dogs and rabbits after hypophysectomy is accom­panied by a greatly increased sensitivity to insulin. This reaction has actually been used by Hartman, Firor, and Geiling (1930) as a test for the completeness of the operation. It is evident, therefore, that, while hypophysectomy cannot be regarded as a necessarily lethal operation in species so far examined, an intensification of the resulting physiological disturbances might lead to a very high mortality. The technique of hypophysectomy of the bird outlined in a previous paper (Hill, R. T., and Parkes (1934)) involves comparatively little damage, so that death from operative manipulation can almost be excluded. We were therefore surprised to find that most fowls died within two days of the operation. This was shown to be a genuine physiological effect by the fact that the mortality could be much reduced by appropriate therapy. The present paper deals with this post-hypophysectomy mortality in the fowl, and with the general effects observed in birds which were carried over the critical period and survived to show chronic pituitary insufficiency.

The effect of ligation of the hepatic artery on carbohydrate metabolism.

Conclusions(1) Ligation of hepatic artery of dogs causes death in hypoglycemic convulsions.(2) The period of survival after ligation depends upon the amount of glycogen previously stored, and varies between 15 to 60 hours.(3) There is a total depletion of glycogen in the tissues at death.(4) Administration of glucose prevents convulsions and prolongs life for several hours.(5) Severing the plexus of nerves surrounding the hepatic artery does not produce this hypoglycemic syndrome.