COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES STANDARD ■•'■■■ '■'..''■■'■i'y „ , • ' QP91 .H7S^'''°°°'uLin.esuga, SUGAR IN THE BLOOD OF PIGEONS RECAP BY HANNAH ELIZABETH HONEYWELL A DISSERTATION Submitted in Partial Fulfillment of the Requirements for the Degree OF Doctor of Philosophy in the Faculty of Pure Science, Columbia University, New York City 1921 Qpq H75. intljeCttpoflrttigork CoIIese of Ij^^psimns mis burgeons Hibrarp STUDIES IN THE SUGAR IN THE BLOOD OF PIGEONS, BY HANNAH ELIZABETH HONEYWELL A DISSERTATION Submitted in Partial Fulfillment of the Requirements for the Degree OF Doctor of Philosophy in the Faculty of Pure Science, Columbia University, New York City 1921 Reprinted from The American Journal of Physiology Vol. 58, No. 1, November, 1921 W7r STUDIES OF THE SUGAR IN THE BLOOD OF PIGEONS HANNAH ELIZABETH HONEYWELL From the Department of Physiology, Columbia University Received for publication July 1, 1921 WTiile it is a recognized fact that much of our experimental data in physiology must be obtained from animals other than man, there has been very little hesitation on the part of many experimenters in drawing conclusions concerning phenomena in man from data derived from other animals. In many cases the results have warranted the practice, in others disappointment has resulted. Actually the larger the number of experiments performed, and the greater the number of species from which the data have been derived, the more justification there is for a generalized statement, and for its application to species other than those upon which work has been done. With this idea in mind it was thought wise to make the determinations leading to the data published in the present paper, on an animal hitherto little used in metaboUsm work. A bird rather than a mammal was chosen largely because of the fact that in this form the red blood corpuscles are nucleated. That this makes a striking difference in the physiology of the blood is well illustrated by Warburg's (1) work on oxygen consump- tion in the drawn blood of birds as compared with that of mammals. The fact that the red corpuscles of birds are nucleated should prove of especial value in studies made on them with the idea of using the re- sults as a means of giving a better understanding of the physiology of the cells of tissues other than blood. A considerable literature has developed upon the exchange of material between the red cells and the plasma. This is especially true of the chlorides and the sugars. The data upon which this literature is based have been obtained from studies on the blood of mammals. It seems probable that parallel studies on bird 's blood with its nucleated cells should lead to a better understanding of this process. The fact that the birds, characteristically, have a higher temperature than mammals is an additional reason why their metabolism should be studied for comparison with that of mammals. In fact, it has been 152 BLOOD SUGAR OF PIGEONS 153 suggested by Bierry (2) that this is the reason for the very high con- centration of sugar found in their blood as compared with that found in the blood of mammals. That there is a correlation between body' temperature and blood sugar concentration is shown by the work of Hollinger (3) and others. Since most of these properties are of general interest the bird should be an instructive addition to our list of laboratory animals. Com- paratively little has been done on the metabolism of birds aside from some work on polyneuritis. It is therefore advisable to extend our knowledge of this phase of their physiology. From birds in general the pigeon was selected and it is thought that it should be a practical and convenient bird with which to work for the following reasons: a, it is of convenient size; h, it is comparatively easy to obtain; c, its first cost is not prohibitive; d, it is easily and economically kept; e, it is a seed eater and therefore herbivorous. Further, in the use of the carrier pigeon there is an opportunity for the study of fatigue. Mosso (4), in fact, has already made some use of it for this purpose. This phase of the work we hope to extend, and con- sequently further data on resting ])irds are necessary for comparison with those obtained from fatigued birds and from resting and fatigued mammals. Method: 1. The care of the birds. The pigeons were confined in the laboratory until they became accustomed to their surroundings. They were subjected to frequent handling in order to reduce their fear of the operator, and so to minimize as far as possible results which might arise from fright. In most cases the birds wholly ceased to resist handling when taken from the cage. During periods between experi- ments the pigeons were kept in a large enclosure giving them oppor- tunity to fly about freely. The food consisted of a mixture of com, . oats, barley and some other grains, and a plentiful supply of fresh water. Access was given to both food and water at all times not otherwise noted. 2. Method of estimation of sugar. MacLean's (5) micro-method was used throughout the research. The macro-method had been success- fully used in this laboratory for other blood sugar determinations. The micro-method possesses the obvious advantage of requiring only a small quantity of blood (0.2 cc). It therefore may be used for animals having a comparatively small amount of blood, and it permits of drawing consecutive samples at relatively short intervals, without pro- ducing serious effects from hemorrhage. The extreme limits of error 154 HANNAH ELIZABETH HONEYWELL were found to be about 10 mgm. per 100 cc. of blood. Variations of this amount or less may, therefore, be disregarded. 3. Special teGhniqiie. While the samples of blood were being drawn the birds were encased in a strong cloth jacket made especially for the purpose. This was done as a matter of convenience to the operator and of safety to the birds. The jacket laced across the ventral surface of the body in such a manner as to be adjustable to birds of varying size, and to secure the wings and legs. The blood was drawn directly from the heart into a 0.2 cc. pipette by means of a long hypodermic needle. This needle was inserted at the end of the breast bone, going directly through the skin and body wall into the abdominal cavity. The tip of the needle followed the breast bone up to the region of the heart, and so avoided puncture of the liver and other viscera. When the heart could be felt at the tip of the needle the point was dropped slightly and plunged into the heart tissue. Following this procedure the needle struck the heart in such a way that arterial blood was drawn. Post-mortem examination showed that the needle usually entered the heart near the apex on the left side. Hj^podermic needles, 20 gauge, and 3 inches long, were used most successfully. Since the distance from the tip of the breast bone to the heart is very neaily equal to the length of such a needle, it is obvious that this method of drawing blood would not be practicable for birds much larger than the pigeon. It is also probable, because of the lesser quantity of blood and the smaller and more delicate heart, that this method would not be applicable to species much smaller. All the experiments were performed during the fall and winter of 1920-21. Study of the concentration of sugar in the blood of indi- vidual BIRDS. It is a common practice in physiological labora- tories to keep the experimental animals for only a short time. While there are probably many cases where repeated observations have been made on individuals, they have not been published with this point in view, and as a result it is difficult to find data showing whether or not the concentration of the sugar in the blood is approximately constant, or whether it is markedly variable from time to time in one animal, and from individual to individual. In order to determine these points for the pigeons, two were set apart to be used exclusively for this study. They were kept in the laboratory throughout the period of ol>servation and had access to food and water at all times. The observations were extended from BLOOD SUGAR OF PIGEONS 155 October 29, 1920 until the death of pigeon A on February 20, and until March 13, 1921 on pigeon B. The first six observations were made at intervals of one week. Following this the intervals were lengthened as indictited in table 1. From this table it will appear that pigeon A, in all but four of the eleven determinations, had a sugar content of 175 mgm. or 180 mgm. per 100 cc. of blood; pigeon B, with four exceptions, 170 mgm. or 175 mgm. per 100 cc. These variations are well within the limits of error for the method, and so are to be considered constant. TABLE 1 Blood sugar of normal birds October 29... November 5. November 13 November 20 December 5 . . December 11. December 18, January 8 . . . . January 15 . . . February 6 . . . February 20 . March 13 Weight grams 317 325 327 330 330 335 335 337 340 337 342 Glucose per 100 cc. mgm. 200 175 175 180 150 180 175 180 175 185 195 Weight grams 368 372 375 380 377 375 370 375 377 375 377 375 Glucose per 100 cc. mgm . 140 170 170 175 215 175 170 170 175 165 190 175 Obviously, then, there is a concentration of sugar which is charac- teristic of the blood of a given bird. The fact, however, that the two birds which happened to be selected yielded characteristic values so close together, does not warrant the extension of this value to other birds, as will appear later. But while it is evident that there is a value which is characteristic of a given bird, it is also evident that this value will not necessarily be obtained at all times. The occa- sional striking variations shown in the table illustrate the fact that here we are dealing with an organism which is responsive to modified condi- tions, and one of its means of adjustment to its environment involves changes in the concentration of blood sugar. This offers experimental confirmation of the statement of Pike and Scott (6) that the concen- tration of sugar in the blood is one of those internal conditions existing THE AMERICAN JOURNAL OF PHYSIOLOGY, VOL. 58, NO. 1 156 HANNAH ELIZABETH HONEYWELL in higher organisms which are generally constant, and which are regulated by the general nervous and physico-chemical mechanisms of the organism as a whole. Three cases offered an opportunity for comparing tlie blood sugar concentration given by individuals at various times after a period of 48 hours' inanition. These data are given in table 2, from which it will be observed that each bird has a value which appears to be characteristic for it. TABLE 2 Blood sugar of individuals after inanition BLOOD SUGAR PER 100 CC. DATE Normal After inanition rngvi. mgm. / 10-11 190 165 ' 1 12-17 175 • { 10-22 185 165 1- 7 185 20 1 11-4 140 100 12-18 135 • TABLE 3 Blood sugar of normal dogs at different times DOG DATE BLOOD SUGAR PER 100 CC. mgm. ^ { 11- 6 75 1- b 73 " { 10-31 67 11- 7 65 = { 11-20 59 1-16 63 These results are similar to those reported by Scott and Hastings (7) for dogs. Two determinations each were made on three different dogs, the greatest difference between consecutive determinations upon the same dog being 4 mgm., as shown in table 3. In a series of 22 blood sugar determinations made by Kramer and Cofl&n (8) on a quiet dog, the amount of glucose varies from 87 mgm. to 93 mgm. per 100 cc, the average being 89 mgm. per 100 cc. BLOOD SUGAR OF PIGEONS 157 Jones (9) states that in making repeated observations on individual rabbits the variations were within the experimental error, and so could be considered as constant. She frequently found, however, a con- siderable variation in passing from individual to individual. In a recent paper Strouse (10) reported a series of observations on five normal persons covering a period of 8 months. In the series the variations for individuals range from 27 mgm. to 59 mgm. per 100 cc. of blood with an average variation of 41 mgm. per 100 cc. Thallinger (11) made repeated observations on a boy with furunculosis, whose blood sugar was abnormally high, varying from 145 mgm. to 155 mgm. per 100 cc. on a liberal diet which was low in carbohydrates. Thus it will be seen that the pigeons agree with the rabbits and dogs in possessing a characteristic sugar value. Strouse 's figures would TABLE 4 Effect of excitement on blood sugar BIRD DATE BLOOD SUGAR PER 100 CC. REMARKS mgm. 4 / I 10- 9 1- 7 185 265 Excited by presence of several strangers 8 { 10-22 10-22 185 300 Excited by loud talking 10 { 11-19 11-20 175 250 Excited by escape from cage indicate that the range may be greater in man, although it is not clear whether this greater range is due to a more ready response to changes in the environment than occurs in the other animals studied, or. whether the sugar-controlling mechanism is not so perfectly developed, or whether possibly the conditions of hving were not so carefully standardized Effect of handlixg; emotional glycemia. As noted in the foregoing, noise, loud talking and the presence of strangers produce a rise in the blood sugar. Rough, sudden or uncertain handling also disturbs the pigeon and increases the blood sugar. In one instance the bird escaped from the cage just before a sample was drawn and some confusion attended its recapture. The amount of sugar in the sample of blood was high, as shown in no. 10, table 4. 158 HANNAH ELIZABETH HONEYWELL From this table it will be seen that the bird offers no exception to the principle long ago pointed out by Boehm and Hoffman (12), Pavy (13) and others, and more recently by Cannon (14), Shaffer (15) and Scott (16), that to obtain blood sugar figures of value, samples of blood must be obtained without pain or other emotional disturbance of the subject. The fact, however, that birds which were known to be ex- cited have such high figures as appear in table 4, indicates that the lower figure of about 185 mgm. per 100 cc. may be assumed to be normal. This was the value obtained by Scott and Honeywell (17) and though Fleming (18) found a much lower value for ducks, in fact a figure quite comparable with that characteristic of mammals, the normal value for the pigeon, at least, appears to be much higher and to agree well with the values published for other birds (cf. Scott and Honeywell). Effect of inanition. For reasons which will be discussed later, the birds were subjected to a 48-hour period of inanition in determining the alimentary glycemia curve to be described in the following section. In all cases the concentration of sugar in the blood was determined soon after the arrival of the birds at the laboratory, and again at the close of the 48-hour fast and just before feeding the glucose. While the effect of this inanition was not the primary purpose of the experiment, this procedure offered opportunity for its study, provided that the initial values can be taken as normal values for birds on full feed. The propriety of this is in some doubt, as the birds had not yet become fully accustomed to their new environment and had not been subjected to standard conditions. This would probably result in rather wide variation from values characteristic for the individual with a general tendency to yield high values. It is felt, however, that the figures as they stand merit some attention. As noted by Rogers (19), the general effect of inanition on the normal pigeon is to increase its natural restlessness. It becomes irritable and fights on the slightest provocation, such as a sudden noise. This might lead one to expect higher blood sugar values in birds subjected to inanition, and may explain those values which are even higher than normal that were occasionally found. From table 5, which contains the data for the blood sugar of pigeons after inanition, it appears that in 36 experiments 19 pigeons show a lower blood sugar after inanition than before. The results vary from 3.1 per cent to 70 per cent below the initial value. Fifteen pigeons ex- hibited an increase in blood sugar ranging from 5 per cent to 100 per cent. Two pigeons showed no change whatever. The entire series BLOOD SUGAR OF PIGEONS 159 TABLE 5 Effect of inanition WEIGHT BLOOD SUGAR PER 100 CC. DATE PERIOD OF INANITION BIRDS Before inani- After inani- Per cent of Before inani- .^fter inani- Per cent of tion tion loss tion tion difference hours grams grams mgm. mgm. 10 November 17 to 19 48 280 250 10.7 200 175 - 8.00 11 November 17 to 19 48 350 320 8.5 175 120 -31.0 12 November 17 to 19 48 300 240 20.0 155 150 - 3.1 13 December 15 to 17 48 300 280 6.6 160 100 -37.6 14 December 15 to 17 48 310 275 11.3 105 90 -14.2 5 December 15 to 17 48 340 325 4.4 190 175 - 7.8 9 January 5 to 7 48 280 272 2.8 140 185 32.0 17 January 5 to 7 48 325 312 4.0 185 265 43.0 18 January 5 to 7 48 300 290 3.3 175 310 77.0 19 January 5 to 7 48 350 330 5.6 150 290 93.0 20 November 2 to 4 48 280 248 11.4 140 100 -28.0 21 November 2 to 4 48 310 280 9.65 120 105 -12.5 22 December 8 to 10 48 330 305 7.6 200 170 -15.0 23 November 10 .to 12 48 340 310 8.8 155 155 0.0 14 November 10 to 12 48 330 315 4.5 105 210 100.0 25 November 10 to 12 48 230 215 6.5 105 170 62.0 26 November 10 to 12 48 290 250 13.8 255 155 -39.0 27 December 2 to 5 48 345 340 1.4 120 150 25.0 28 December 2 to 5 48 330 305 7.6 150 140 - 6.6 29 December 8 to 10 48 365 340 6.8 120 175 46.0 8 December 16 to 18 48 3;3'0 300 9.1 185 55 -70.0 9 December 16 to 18 48 300 262 12.6 140 135 - 3.5 4 December 16 to 18 48 300 290 3.3 185 100 -46.9 33 December 20 to 22 48 340 330 2.9 160 175 9.4 12 December 20 to 22 48 330 317 3.9 155 155 0.0 11 December 20 to 22 48 300 285 5.0 175 150 -14.2 36 December 19 to 21 48 300 280 6.7 185 110 -40.6 37 December 19 to 21 48 300 285 5.0 190 160 -15.8 38 December 19 to 21 48 380 340 10.5 185 115 -37.9 9 December 19 to 21 48 350 340 2.8 140 180 28.6 2 September 11 to 14 48 220 195 11.3 290 300 3.4 3 September 11 to 14 48 216 200 7.4 190 200 5.2 8 October 20 to 22 48 356 300 15.7 185 200 8.1 9 October 20 to 22 48 360 280 22.2 187 165 -11.7 51 October 20 to 22 48 330 272 17.6 195 205 5.1 52 November 2 to 4 48 340 320 5.9 140 160 14.3 Aver age 166 165 - 0.6 *^o^ • 160 HANNAH ELIZABETH HONEYWELL gave an iaverage decrease in blood sugar of 0.6 per cent. It may, therefore, be that 48 hours inanition has practically no effect on the blood sugar of the pigeon. As pointed out above, the evident irri- tabihty of the birds subjected to inanition with its possible effect upon the concentration of sugar in the blood should be borne in mind. Effect of ingestion of glucose: 1. Special technique and dis- cussion. As noted in the previous section, the sugar was determined upon the arrival of the birds in the laboratory. Also as described above, after the birds had become accustomed to the laboratory, they were subjected to a fast of 48 hours and the sugar in the blood again determined. The results of these two . determinations were given in table 5. In addition to the reasons usually assigned for a preliminary period of inanition, this somewhat prolonged period seemed to be necessary to empty the crop and so to insure a rapid passage of the sugar to the region of the alimentary tract where absorption might be expected to take place. It will be readily appreciated that this is even more essential in the case of such birds as the pigeon, which are pro- vided with crop and gizzard, neither of which is presumably a region of absorption, than it is with the mammals, and possibly than it would be with other birds. The alimentary canal was empty in all birds examined, so this period of inanition may be considered as sufficient to fulfill its purpose. After the second sugar determination, the appropriate amount of glucose was administered. To facilitate the feeding, the glucose was made into tablets and a weighed amount, 1, 2 or 3 grams, according to the series, was given to each bird. In feeding the sugar, the beak was opened and the tablets were dropped well back into the haouth. If the pellets were not readily swallowed, a little water was given through a dropper. Sometimes gentle stroking of the throat seemed to aid when swallowing wa§ especially slow. Three series of experiments were carried out. In series I, each pigeon was fed 1 gram of glucose;. in series II, 2 grams; and in series III, 3 grams. In terms of grams per kilogram of body weight, the average amount of glucose fed was 4 grams, 7 grams, and 10 grams in the respective series. The ordinary clinical test for carbohydrate tolerance is 100 grams or about 1.4 grams per kilogram of body weight, if the average weight for man is taken to be 70 kilograms. This amount was fed by Cummings and Piness (20), Hiller and Mosenthal (21), Jacobsen (22), Tachau (23) and Strouse, who has also fed 2 grams and 2.8 grams per kilo to normal men. Jones gave rabbits an average dose of 7.87 grams per kilogram. BLOOD SUGAR OF PIGEONS 161 From the foregoing it will be seen that the amounts given to the pigeon exceed those usually given man in similar experiments. In spite of this, the smallest dose used in the present experiments which is equivalent to one of 1 .75 grams for a man weighing 70 kilograms, had very little effect on the concentration of sugar in the blood of the pigeon. In a man such an amount would in all probability raise the concentration of blood sugar to 200 mgm., and probably induce gly- cosuria. 2. Time of the maximimi. Since it was desired to determine the principal points in the entire curve, that is, to follow the curve to its return to the initial value, and since the number of samples of blood which could be drawn safely in any one experiment was limited be- cause of the injury to the heart which would result from repeated TABLE 6 Time of maximum of alimentary glycemia BLOOD SUGAR BLOOD SUGAR PER 100 CC. AFTER FEEDING GLUCOSE BIRD GLUCOSE FED AFTER INANITION 1 hour 2 hours 3 hours 4 hours 5 hours grams mgm. mgm. mgm. mgm. mgm. 61 3 160 155 240 400 335 320 62 3 180 185 235 305 210 215 64 2 210 205 245 315 275 260 65 2 185 200 215 240 250 205 66 1 170 190 200 215 240 200 67 1 165 170 185 205 225 190 punctures at short intervals, it was necessary to determine the time elapsing between the administration of the glucose and the maximum sugar concentration in the blood. For this purpose, as indicated in table 6, hourly determinations were made after the sugar was fed. It will be seen from the results given in this table that the maximum may be assumed to occur between the third and -fourth hours. This last interval was therefore allowed to elapse after feeding and before drawing the first sample, and the sugar level at this time may be assumed very nearly to represent the maximum attained. When 3 grams of glucose were fed the maximum occurred at or about the third hour. When 2 grams of glucose were fed the maximum occurred in one case at the third hour and in the other case at the fourth hour. After the feeding of 1 gram of glucose, the maximum occurred at about the fourth hour. From these results, given in table 6, it will 162 HANNAH ELIZABETH HONEYWELL appear that the greater the amount of glucose fed the earlier the maxi- mum will be reached. In this connection it is interesting to note, as Strouse has pointed out, that a heavy dosage often has the effect in man of delaying the onset of the maximum rather than accelerating it as in the pigeon. There must be, then, some fundamental difference between the carbohydrate economy of the pigeon and that of man. 3. Course of alimentary hyperglycemia. In each case samples of blood were drawn just before the administration of the glucose and again after the lapse of 4, 6 and 24 hours. The results are collected in J.GO l¥ tables 7, 8 and 9 and summarized in the accompanying curves (fig. 1). In the first series one gram of glucose was given each bird. As noted before, this is about double the ratio of the test meal usually given man for diagnostic purposes. From table 7 it will appear that there is no change or as occurs more frequently, only a slight rise at the end of the first period. The average for the series gives a rise of 18 per cent at this time. In the second and third series there is a different manifestation. In the second series 2 grams, and in the third 3 grams were given each bird. The average rise at the end of 4 hours in the second series was 45 per cent, and in the third, 93 per cent. From table 8 it will be seen that BLOOD SUGAR OF PIGEONS 163 m the second series only five birds had returned to their previous level at the end of 24 hours; and in the third series, table 9, one alone had returned in that interval to the level which existed before the ingestion of the glucose. While the average at the end of the inanition period may vary some- what for the different groups, the average at the end of 24 hours after feeding the glucose is approximately that of the normal birds. Be- cause of the relatively low initial values found in the second and the third series, the final values found for these series are distinctly higher TABLE 7 Effect of ingestion of glucose upon the sugar in the blood Series I GLU- BLOOD SUGAR PER 100 CC. COSE AFT EI I FEEDING GLUCOSE BIRD DATE WEIGHT FED PER KILO OF IN- CREASE REMARKS Inani- tion 4 hours 6 hours 24 hours grams (jrams mgm. mgm. mgm. mgm. 10 November 19 250 4.0 175 100 110 250 -37.0 Bird excited by 11 November 19 320 3.1 120 150 150 125 25.0 escape from 12 November 19 240 4.2 155 150 160 150 3.2 cage before 13 December 17 ■ 280 3.5 100 275 245 195 175.0 drawing of 24 14 December 17 275 3.6 90 210 300 270 233.0 hour sample 5 December 17 325 3.1 175 170 160 230 - 2.8 9 January 7 272 3.7 185 270 175 265 46.0 17 January 7 312 3.2 265 280 275 275 5.7 18 January 7 290 3.4 310 350 300 250 1.3 19 January 7 330 3.0 290 295 260 155 1.7 Average 259 3.9 190 225 175 180 18.0 than the initial values. Whether or not this is significant we are not prepared to state definitely, although it would seem to be accidental. Unfortunately there is very little data available which permits of a comparison of the course of the alimentary hyperglycemia of different species. In fact, only three species seem to have been studied from this point of view. In her recent paper, Jones has made determinations on the blood of rabbits only at a single period after the ingestion of the glucose. From the work of Bang (24), the 1-hour period which she chose would presumably give figures at or near the maximum attained. Her results do not, however, permit one to follow the course of the curve. Bang reported a short series of experiments on rabbits which had been 164 HANNAH ELIZABETH HONEYWELL fed from 5 to 20 grams of glucose. After a S-daj^ period of inanition he found that the maximum was reached in 1| to 2^ hours, and that in general the sugar level had returned to normal in 6 hours. The amount of sugar did not seem materially to modif}^ the time relations of the curve. The same may be said of a similar but even shorter series, in which sugar was given without a previous period of inanition. Fisher and Wishart (25) in experimenting with dogs weighing 8 to 9 kilograms, fed approximately 6 grams of glucose per kilogram, and found that the maximum blood sugar occurred one hour after the ingestion of the glucose. TABLE 8 Series II BIRD DATE WEIGHT GLUCOSE FED PER KILO BLOOD SUGAR PER 100 CC. . FEEDING GLUCOSE A.FTER PER CENT OF IN- Inani- tion 4 hours 6 hours 24 hours CREASE grams grams Tngm. mgm. mgm. mgm. 20 November 4 248 8.4 100 150 125 295 50.0 21 November 4 280 7.1 105 300 250 180 185.0 22 December 10 305 6.5 170 290 280 2b0 70.0 23 November 12 310 6.4 155 440 140 145 184.0 14 November 12 315 6.3 210 210 ■ 250 240 19.0 25 November 12 215 9.3 170 200 190 120 17.0 26 November 12 250 8.0 155 250 210 160 61.0 27 December 4 340 5.9 150 280 100 130 87.0 28 December 4 . 305 6.5 140 200 285 175 103.0 29 December 10 340 5.9 175 270 160 110 54.0 Aven lee 290 6.9 165 240 195 180 45.0 The work of many investigators, notably Cummings and Piness, Hiller and Mosenthal, Hamman and Hirschman (26), Jacobsen and Strouse, indicates that after the ingestion of 100 grams of glucose the maximum concentration of sugar in the blood of man occurs normally in about 30 minutes and that it has returned approximately to its previous level by the end of the second hour. Jacobsen and Strouse point out that occasionally the maximum is attained only after a longer period; and that when this is true the level is apt to be higher than usual, and the return to the previous value is usually slower. Strouse particularly calls attention to the fact that in diabetes and other conditions which may be presumed to alter the carbohydrate metabolism, such curves are common but that such individuals may be BLOOD SUGAR OF PIGEONS 165 induced to give the ''normal" or usual curve if given less sugar. On the other hand normal individuals will give the ''diabetic" curve if the dose be doubled or tripled. A study of the curves obtained from pigeons shows that the maximum occurs from the third to the sixth hour after feeding, and when amounts were fed which essentially altered the sugar level, the curve did not return to normal for a much longer period, in some cases exceeding 2-4 hours. Thus they resemble more closely the delayed curves ob- tained from men rather than the usual or normal one, and, at first thought, the obvious reason is the very heavy dose of glucose given to the birds. TABLE 9 Series III GLU- COSE BLOOD SuUaR per 100 CC. AFTER FEEDING GLUCOSE PER 1 BIRD DATE WEIGHT FED PER KILO 1 OF IN- CREASE REMARKS Inani- tion 4 hours 6 hours mgm. 24 hours grams grams mgm. mgm. mgm. 8 December 18 300 10.0 55 215 200 205 291.0 20 December 18 262 11.4 135 320 150 160 137.0 Excited by pres- 4 December 18 290 10.3 100 160 300 22Q 200.0 ence of strangers 33 December 20 330 9.0 175 335 200 110 91.5 when third sam- 12 December 20 317 9.4 155 240 210 225 55.0 ple was shown. 11 December 20 285 10.5 150 320 195 175 113.0 Struggled and died 36 December 21 280 10.7 110 225 205 260 104.5 during drawing 37 December 21 285 10.5 160 200 265 180 65.5 of last sample. 38 December 21 340 8.8 115 265 110 195 130.4 9 December 21 340 8.8 180 330 220 205 210 180 84.0 Average 303 9.8 1 135 260 93.0 In order to determine this point, that is, whether the pigeons would respond to a smaller dose and whether or not a maximum occurring during the first hour had been overlooked, four birds were fed 0.4 gram of glucose each, after an inanition period of 48 hours. This is the amount of glucose which, for the weight of the bird, approximates the usual test dose for man. Blood sugar determinations were made 30 minutes, 1 hour and If hours after the ingestion of the glucose. The results are shown in table 10. Since the variations were all within the limits of experimental error, it may be concluded that the pigeon does not respond to as small a dose as does man and that there is a fundamen- tal reason for the difference in the alimentary glycemia curves shown by the two species. 166 HANXAH ELIZABETH HONEYWELL In his series on normal men Strouse obtained an average increase of 42 per cent after an ingestion of 100 grams of glucose, or 1.4 grams per kilogram. The pigeons show an average increase of only 18 per cent after the ingestion of 1 gram or about 3.5 grams per kilogram, and it was not until they had been given 2 grams or 7 grams per kilogram that they approached the percentage increase reported by Strouse for men. In addition it should, perhaps, be pointed out that the resemblance is more apparent than real for, as mentioned above, the effect of the size of the dose upon the time elapsing between the administration of the dose and the occurrence of the maximum is in the opposite sense in the pigeon and in man. It would thus seem that the mechanism of storage of sugar is somewhat different in the two groups. Post-mortem examinations of two pigeons which were killed after inanition and before feeding showed that the crop and gizzard were TABLE 10 Effect of varying amounts of glucose on time of maximum BIRDS WEIGHT AMOUNT OF GLUCOSE FED BLOOD SUGAR IN MGM. PER 100 CC. FEEDING GLUCOSE AFTER PER KILO Inanition h hour 1 hour U hours grams grams 1 250 1.6 180 165 180 175 2 370 1.1 220 225 230 225 3 280 1.4 195 200 190 205 4 350 1.1 185 175 180 175 empty, while the intestine contained only a small amount of fluid. Conditions were the same in pigeons which were examined at the end of the fourth and sixth hour after feeding. The contents of the ali- mentary tract were not tested for the presence of sugar. Conse- quently, while the indications as they stand are that the delay in reaching the maximum is not due to delay in absorption, but rather to some peculiarity in the mechanism of storage, one is not justified in definitely drawing such a conclusion until a study of the contents of the alimentary canal has been made in parallel with blood sugar deter- minations. Since concentration of the sugar in the bird is normally so high as compared with mammals, in this particular resembling the diabetic, and since the curve obtained from birds somewhat resembles that ob- tained from diabetic man, there may possibly be some relationship be- BLOOD SUGAR OF PIGEONS 167 tween the absolute initial height of the sugar concentration and the form of the curve of alimentary hyperglj^cemia. However, as noted above, it would seem more probable that in the birds the storage mechanism is somewhat different from that common in mammals and that further work must be done before a satisfactory correlation is possible. SUMMARY 1. Each bird has a characteristic sugar level about which it varies from day to day. In this it resembles the rabbit and dog. 2. These individual variations are caused by variations in the ex- ternal and internal environment of the bird. 3. A series of inanition values for blood sugar is given and com- pared with the values found on full diet. From these figures it is concluded that 48 hours' inanition has practically no effect on the blood sugar of the pigeon. 4. It has been found that, in general, when from 1 to 3 grams of glucose are fed to the pigeon the maximum rise in the blood sugar occurs in 3 to 4 hours. 5. It is indicated that the greater the amount of glucose given the earlier will the maximum be reached. 6. When 1 gram of glucose or less is fed to pigeons there is very little modification of the sugar in the blood. When 2 or 3 grams are fed there is a manifest rise in the blood sugar which gradually approaches its former level. The author wishes to acknowledge her indebtedness to Prof. E. L. Scott for his assistance in the execution of this work. BIBLIOGRAPHY Warburg: Hoppe-Seyler's Zeitschr., 1910, Ixvi, 305; Ixxvi, 331. Bierry: Comptes Rendus, 1919, clxix, 1112. Hollinger: Deutsche. Arch. f. klin. Med., 1908, xcii, 217. Mosso: Fatigu, New York, 1904. MacLean: Biochem. Journ., 1919, xiii, 135. Pike and Scott: Amer. Naturalist, 1915, xHv, 321. Scott and Hastings: Proc. Soc. Exper. Biol, and Med., 1920, xvii, 67. Kramer and Coffin: Journ. Biol. Chem., 1916, xxv, 423. Jones: Journ. Biol. Chem., 1920, xliii, 507. Strouse: Arch. Int. Med., 1920, xxvi, 751. Thallinger: Journ. Amer. Med. Assoc, 1921, Ixxvi, 295. 168 HANNAH ELIZABETH HONEYWELL (12) BoEHM AND Hoffmann: Arch, f, Exper. Path. u. Pharm., 1878, viii, 271. (13) Pavy: Journ. Physiol., 1899, xxiv, 479. (14) Cannon : This Journal, 1914, xxxiii, 356. (15) Shaffer: Journ. Biol. Chem., 1914, xix, 285. (16) Scott: This Journal, 1914, xxxiv, 271. (17) Scott and Honeywell: This Journal, 1921, Iv, 362. (18) Flemming: Journ. Physiol, 1920, liii, 236. (19) Rogers: This Journal, 1916, xli, 555. (20) CmiMiNGS AND PiNESs: Arch. Int. Med., 1917, xix, 777. (21) HiLLER AND MosENTHAL : Joum. Biol. Chem., 1917, xxviii, 197. (22) Jacobsen: Biochem. Zeitschr., 1913, Ivi, 471. (23) Tachau: Arch. f. klin. Med., 1911, civ, 437. (24) Bang: Der Blutzucker, 1913. (25) Fisher and Wishart: Journ. Biol. Chem., 1912, xiii, 49. (26) Hamman and Hirschmann: Arch. Int. Med., 1917, xx, 761. VITA Hannah Elizabeth Honeywell was born in Walton, N. Y., April 3, 1888. She graduated from Walton High School in 1906, received the degree of Batchelor of Arts from Mount Holyoke College in 1910, and the degree of Master of Arts from Columbia in 1917. Her publications are: A Study of the Sugar in the blood of Normal Pigeons. (With E. L. Scott.) American Journal of Physiology, 1921, Iv, 362. COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the rules of the Library or by special arrange- ment with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE C2e(l14l)M100 QP91 H75 Honeywell