Relation between Blood Sugar and Tissue Sugar 1

Transcription

1 Relation between Blood Sugar and Tissue Sugar 1 By Svein Lunde Sveinsson (From the Physiological nstitute of the University of Oslo) (With figure in the text) When working with balance experiments concerning the carbohydrate metabolism the question often arises as to what quantity of glucose corresponds to a definite variation in the blood sugar. n the course of an experiment the blood sugar may, for example, have increased to some extent while at the same time the content of glycogen in the liver has decreased. t is possible to calculate the loss of glycogen in the liver, given the weight of the liver. f we would compare this amount of glycogen with the observed increase in blood sugar, the difficulty here presents itself that we do not know what amount of glucose corresponds to a certain increase in the blood sugar. All experiments contradict the supposition that the blood sugar level is an indication only of the amount of glucose within the blood vessels. The rise in blood sugar following immediately upon an intravenous injection of glucose is very much less than would be expected if the glucose had mixed onlywith theblood. A diffusion of glucose into the tissues must obviously take place immediately after an injection of glucose. The question now arises whether a definite relation exists between the increase in the amount of glucose taking place in the blood vessels and the amount that passes into the tissues. f such a definite relation exists, variations in the blood sugar might perhaps serve as a measure for variations in the total quantity of glucose in the organism. Little attention has been paid to this matter. A number of authors have tried to determine the amount of glucose in the different tissues by extraction methodes. Cori and Goltz ( ) injected an amount of sugar intravenously in fasting mice and determined afterwords the content of sugar in the blood and in the liver and muscles. l Received for publication 15 November 19.

2 RELATON BETWEEN BLOOD SUGAR AND TSSUE SUGAR 189 They found that an equilibrium between the sugar concentration of the blood and the liver is reached minute after the start of the injection. n case of the muscles this equilibrium is reached a little later. Cori (1931) emphazises that the estimation of sugar by extraction methodes entails a danger on the one hand of glycogenolysis which occurs very rapidly post mortem or in excised samples of tissue and on the other hand of some reducing non-sugar substances being extracted together with the glucose. Burn and Dale (1924) wished to deduce the total amount of sugar circulating in a decapitated and eviscerated cat from the content of sugar in a blood sample. They infused at a constant rate a 4 p. c. solution of dextrose until the blood sugar became steady. After half an hour at this rate the infusion was suddenly accelerated. The increase in the amount of glucose injected during S min. at this new rate of infusion is compared with the rise in blood sugar oberved in the same time, and the authors found in one preparation of 3 kilos. weight that the glucose must have been distributed in an amount of fluid (in blood, lymph and tissue spaces) = 500 ml. Cori has tried to simplify the mode of procedure for the estimation of the tissue sugar in rats and mice. After a blood sample had been taken for determination of the content of sugar, the animals were killed and the total amount of glucose was determined by extraction. He found that both in rats and in mice the concentration of sugar in the blood was about twice as great as in the whole animal. With the same concentration of sugar as in the blood the total content of sugar in the organism would accordingly be contained in a quantity of tissue corresponding to about 50 per cent of the body weight. Cori asserts therefore that the quantity of sugar present in the tissues may be determined fairly accurately if the blood sugar is known. Such a mode of procedure cannot be used in case of larger animals. The author has set himself the task of investigating whether any correlation can empirically be found between the amount of glucose in the organism and the sugar concentration in the blood. The blood sugar after a rapid intravenous injection will rise quickly until, 1-2 minutes after the termination of the injection, it becomes stable at a definite level, from which it in the course of some time declines to normal. t might be supposed that the glucose diffuses quickly from the blood vessels in the tissues until after 1-2 minutes an equilibrium between blood and tissue is reached. After this time the concentration of sugar in blood and tissue gradually declines owing to the conversion and combustion of sugar. The author has put forward the question whether the rise in the concentration of sugar in the blood after an injection of a known quan-

3 190 SVEN LUNDE SVENSSON Table Experiments with ntravenous njection of Glucose or Galactose to Rabbits, a mg per kg Body We i g h t, Blood Sugar before njection B. Blood Sugar after njection B 2 Rabbitt No. and Exp. No a 8a 9 loa la "c 12a "c Date ?? Quantity of sugar Rise in blood Weight injected reckoned of ani- per kg' of body sugar in mg per mal weight in mg (a) cent (B2 - B ) n g GlucoseGalactose GlucoseGalactose, , a B _ B Remarks ". rvoninarcotized, r Pernocton narcosis tity of glucose has any definite relation to the quantity injected. To investigate this matter known amounts of glucose were injected rapidly.into the marginal vein of one ear. The blood sugar which was determined before the injection, was now determined by frequent analyses from

4 RELATON BETWEEN BLOOD SUGAR AND TSSUE SUGAR 191 the marginal vein of the other ear in the first 4-5 minutes after the injection. The rise in blood sugar found was considered in relation to the amount of glucose injected and to the weight of the animal. The experiments were first performed on animals to which no narcotic had been given. They were later performed on pernocton-narcotized animals in order to minimize the possibility of errors due to endogenous increase in the blood sugar (adrenalin effect). Pernocton is a narcotic which has been found to have very little influence on the blood sugar (Sveinsson, 1936). n some cases different amounts of glucose were injected into the same animals at different times. Finally, in some experiments galactose was injected, and the content of galactose in the blood was determined by a method described by Larsson and Sveinsson (19). The reason for using galactose was also to avoid errors due to endogenous increase in the content of glucose in the blood (from glycogen in liver and muscles) during the injection. The increase in the quantity of galactose in the blood was determined by estimating before the injection the residual reduction + blank expressed as galactose, and after the injection the residual reduction + blank + the galactose content expressed as galactose and by then taking the difference between these two. f the concentration of sugar in the blood before the injection expressed in mg per cent is represented by B and the sugar concentration after the injection at the above stated level E 2, then B 2 - B will express the increase in the sugar concentration in the blood after the sugar injection. f the number of mg sugar injected per kg of body weight be called a, we have to investigate whether a definite relation a exists between a and B 2 - B, in other words whether is B 2-B fairly constant in the case of the experimental animals. The relation obviously expresses how many times greater is the amount of sugar, distributed in the organism per kg body weight expressed in mg than the increase in the blood sugar expressed in mg per cent which has been brought about by the amount of sugar administered. The results will be seen from the table and diagrams (Fig. r). The table shows that the relationship between the quantity of glucose injected and the increase in the blood sugar is fairly constant, especially in the case of the narcotized animals where the. danger of disturbances by an endogenous increase in the blood sugar is least. The relationship in these animals varies between 2.x6 and 3.05 and accordingly shows a fairly constant value. t must, however, be emphasized that it is not always easy to fix exactly the blood sugar level which is reached after an injection and this is especially so with regard to the galactoseexperiments where it has not been possible to take so frequent blood

5 192 SVEN LUNDE SVE~SSO~ [XP3 :~ G-Wc. \.~ EXP'8B G.oc , MN. [XPA.:~. o J 5 MN. EX? le GLLle. of 2 3 't 5 bmn 'f 5 MN...-. EX!! 12A GAL ACT. EX? 128.~ GWc. 0 of 3 't 5, MN. 0 of 2 J 't timn. XP.13A &ALACT....' EXf!138 eeoc. o 1 Z 3 t smn. Diagrams illustrating some of the experiments reported in the table. ntravenous injection of a mg sugar per kg body weight at the point of time o. Blood sugar level before injection = B 1 and blood sugar level after injection = B 2 B 2-B1 = rise in blood sugar analyses. The errors which may occur for this reason will not, however, be very great. As mentioned above few experiments of this nature have been recorded. Corley (1927) has, however, for another purpose injected rabbits with known quantities of galactose, and has estimated the sugar content in the blood before and also two minutes after the injec-

6 RELATO:" BETWEEN BLOOD SUGAR AND TSSUE SUGAR 193 tion. Reckoned on this single analysis two minutes after the injection the relationship between the quantity of galactose injected and the increase in the blood sugar will be found to be considerably greater than in the authors own experiments, ranging, as they do, from 4 to 6. lt is, however, possible to explain this difference between two groups of animals of the same kind. The calculation of the rise in blood sugar in relation to the total body weight is not an ideal method. Large parts of the body weight are of little or no importance with regard to the distribution of the injected sugar. These include the fur, fatty tissue and the considerable content of the alimentary tract which can make up a different percentage of the total weight of various groups of the same kind of animal, dependent among other things upon the treatment they have received. t appears from the experiments performed that in a group of similarly treated animals of the same kind (rabbits) a fairly definite relation exists between the amount of sugar intravenously injected (reckoned per kg of body weight) and the subsequent rise in the blood. increase in tissue sugar. sugar. The quotient seems to be fairly constant. increase in blood sugar The question arises whether we can make the converse statement that a certain increase in the blood sugar corresponds to some degree to a definite increase in the total content of sugar in the organism. Such a statement seems not illogical if the distribution of glucose in the organism proceeds in accordance with osmotic laws. Summary An attempt is made to determine the extent of the variations taking place in the total content of sugar in the organism when the sugar content in the blood varies. The mode of procedure has been to investigate whether a fairly definite relation exists between the amount of glucose injected reckoned per kg body weight and the rise in blood sugar taking place. For a group of similarly treated rabbits this relation is found to vary between 2 and 3, the amount of glucose injected reckoned per kg body weight being expressed in mg and the rise in blood sugar in mg per cent. t is considered possible to use these figures for a statement in the reverse direction concerning these particular animals, namely from the rise in blood sugar observed to the increase taking place in the total content of sugar in the organism.

7 194 SVEN LUNDE SVENSSON, RELATON BETWEEN BLOOD SUGAR ETC. References Burn,. H. and H. H. Dale, J. Plzysiol Cori, c. F., Plzysiol. Rev Cori, C. F. and H..L. Goltz, Proc. Soc. expo Bioi.,Y. Y Corley, R. C., J. Bio. Chem Larsson, P. A. and S. L. Sve i n s s o n, This Archiv Sveinsson, S. L., bidem