Relation between Blood Sugar and Tissue Sugar

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<ul><li><p>Relation between Blood Sugar and Tissue Sugar 1By</p><p>Svein Lunde Sveinsson</p><p>(From the Physiological Institute of the University of Oslo)(With I figure in the text)</p><p>When working with balance experiments concerning the carbohy-drate metabolism the question often arises as to what quantity ofglucose corresponds to a definite variation in the blood sugar. In thecourse of an experiment the blood sugar may, for example, have in-creased to some extent while at the same time the content of glycogenin the liver has decreased. It is possible to calculate the loss of glycogenin the liver, given the weight of the liver. If we would compare thisamount of glycogen with the observed increase in blood sugar, thedifficulty here presents itself that we do not know what amount ofglucose corresponds to a certain increase in the blood sugar. All experi-ments contradict the supposition that the blood sugar level is an indica-tion only of the amount of glucose within the blood vessels. The risein blood sugar following immediately upon an intravenous injection ofglucose is very much less than would be expected if the glucose had mixedonly with the blood. A diffusion of glucose into the tissues must obviouslytake place immediately after an injection of glucose. The question nowarises whether a definite relation exists between the increase in theamount of glucose taking place in the blood vessels and the amountthat passes into the tissues. If such a definite relation exists, variationsin the blood sugar might perhaps serve as a measure for variationsin the total quantity of glucose in the organism.</p><p>Little attention has been paid to this matter. A number of authorshave tried to determine the amount of glucose in the different tissuesby extraction methodes. Cori and Goltz (1925-26) injected anamount of sugar intravenously in fasting mice and determined after-words the content of sugar in the blood and in the liver and muscles.</p><p>l Received for publication 15 November 1939.</p></li><li><p>RELATION BETWEEN BLOOD SUGAR AND TISSUE SUGAR 189</p><p>They found that an equilibrium between the sugar concentration ofthe blood and the liver is reached I minute after the start of the injec-tion. In case of the muscles this equilibrium is reached a little later.Cori (1931) emphazises that the estimation of sugar by extractionmethodes entails a danger on the one hand of glycogenolysis whichoccurs very rapidly post mortem or in excised samples of tissue andon the other hand of some reducing non-sugar substances being extractedtogether with the glucose. Burn and Dale (1924) wished to deducethe total amount of sugar circulating in a decapitated and evisceratedcat from the content of sugar in a blood sample. They infused at a con-stant rate a 4 p. c. solution of dextrose until the blood sugar becamesteady. After half an hour at this rate the infusion was suddenly accele-rated. The increase in the amount of glucose injected during IS min. atthis new rate of infusion is compared with the rise in blood sugar obervedin the same time, and the authors found in one preparation of 3 kilos.weight that the glucose must have been distributed in an amount offluid (in blood, lymph and tissue spaces) = 500 ml. Cori has tried tosimplify the mode of procedure for the estimation of the tissue sugarin rats and mice. After a blood sample had been taken for determinationof the content of sugar, the animals were killed and the total amountof glucose was determined by extraction. He found that both in ratsand in mice the concentration of sugar in the blood was about twiceas great as in the whole animal. With the same concentration of sugaras in the blood the total content of sugar in the organism would accor-dingly be contained in a quantity of tissue corresponding to about 50 percent of the body weight. Cori asserts therefore that the quantity ofsugar present in the tissues may be determined fairly accurately if theblood sugar is known.</p><p>Such a mode of procedure cannot be used in case of larger animals.The author has set himself the task of investigating whether any corre-lation can empirically be found between the amount of glucose in theorganism and the sugar concentration in the blood. The blood sugarafter a rapid intravenous injection will rise quickly until, 1-2 minutesafter the termination of the injection, it becomes stable at a definitelevel, from which it in the course of some time declines to normal.It might be supposed that the glucose diffuses quickly from the bloodvessels in the tissues until after 1-2 minutes an equilibrium betweenblood and tissue is reached. After this time the concentration of sugarin blood and tissue gradually declines owing to the conversion andcombustion of sugar.</p><p>The author has put forward the question whether the rise in theconcentration of sugar in the blood after an injection of a known quan-</p></li><li><p>190 SVEIN LUNDE SVEINSSON</p><p>Table IExperiments with Intravenous Injection of Glucose or Galac-tose to Rabbits, a mg per kg Body We i g h t, Blood Sugar before In-</p><p>jection BI . Blood Sugar after Injection B 2</p><p>RabbittNo.andExp.No.</p><p>Date</p><p>. Quantity of sugar Rise in bloodWeight injected reckonedof ani- per kg' of body sugar in mg per</p><p>mal weight in mg (a) cent (B2 - BI )In g I IGlucose Galactose Glucose Galactose,</p><p>,</p><p>a IB _ B I Remarks</p><p>2 I II</p><p>1600 I 446I</p><p>2</p><p>3</p><p>456</p><p>7a</p><p>"b8a"b9</p><p>loa</p><p>"b</p><p>lIa</p><p>"b"c</p><p>12a</p><p>"b"c</p><p>"b</p><p>22-10</p><p>3723-10</p><p>3725-10</p><p>3726-1037</p><p>??</p><p>25-139</p><p>9-539</p><p>20-539</p><p>26-539</p><p>3-539</p><p>16-539</p><p>9-539</p><p>20-539</p><p>3-539</p><p>16-539</p><p>5-539</p><p>20-5</p><p>1545</p><p>24452165244534</p><p>2822</p><p>2780</p><p>277</p><p>297</p><p>2900</p><p>3435</p><p>335</p><p>27</p><p>2720</p><p>2935</p><p>2900</p><p>325</p><p>315</p><p>315</p><p>2727</p><p>312</p><p>55</p><p>328</p><p>29</p><p>299299</p><p>172</p><p>1611591158065</p><p>128117</p><p>129</p><p>118</p><p>112</p><p>116</p><p>125</p><p>116</p><p>112</p><p>194</p><p>109</p><p>106</p><p>118</p><p>9999</p><p>259</p><p>5.09</p><p>2.28</p><p>3.0 0</p><p>3333. 13</p><p>3-4 12.092372592.88</p><p>2.52</p><p>2.60</p><p>3.0 1</p><p>2.67</p><p>2.81273</p><p>2332.16</p><p>3.05</p><p>2.88</p><p>3.0 23.0 2279</p><p>I ".I rvon-inarcotizedII,</p><p>IIr</p><p>Pernoctonnarcosis</p><p>tity of glucose has any definite relation to the quantity injected. Toinvestigate this matter known amounts of glucose were injected rapidly</p><p>.into the marginal vein of one ear. The blood sugar which was determinedbefore the injection, was now determined by frequent analyses from</p></li><li><p>RELATION BETWEEN BLOOD SUGAR AND TISSUE SUGAR 191</p><p>the marginal vein of the other ear in the first 4-5 minutes after theinjection. The rise in blood sugar found was considered in relation tothe amount of glucose injected and to the weight of the animal. Theexperiments were first performed on animals to which no narcotic hadbeen given. They were later performed on pernocton-narcotized animalsin order to minimize the possibility of errors due to endogenous increasein the blood sugar (adrenalin effect). Pernocton is a narcotic whichhas been found to have very little influence on the blood sugar (Sveins-son, 1936). In some cases different amounts of glucose were injectedinto the same animals at different times. Finally, in some experimentsgalactose was injected, and the content of galactose in the blood wasdetermined by a method described by Larsson and Sveinsson(1939). The reason for using galactose was also to avoid errors due toendogenous increase in the content of glucose in the blood (from glycogenin liver and muscles) during the injection. The increase in the quantityof galactose in the blood was determined by estimating before theinjection the residual reduction + blank expressed as galactose, andafter the injection the residual reduction + blank + the galactosecontent expressed as galactose and by then taking the difference betweenthese two. If the concentration of sugar in the blood before the injectionexpressed in mg per cent is represented by BI and the sugar concen-tration after the injection at the above stated level E 2, then B2 - BIwill express the increase in the sugar concentration in the blood afterthe sugar injection. If the number of mg sugar injected per kg of bodyweight be called a, we have to investigate whether a definite relation</p><p>aexists between a and B2 - BI , in other words whether isB2-BIfairly constant in the case of the experimental animals. The relationobviously expresses how many times greater is the amount of sugar,distributed in the organism per kg body weight expressed in mg thanthe increase in the blood sugar expressed in mg per cent which hasbeen brought about by the amount of sugar administered.</p><p>The results will be seen from the table and diagrams (Fig. r).The table shows that the relationship between the quantity of glucoseinjected and the increase in the blood sugar is fairly constant, especiallyin the case of the narcotized animals where the. danger of disturbancesby an endogenous increase in the blood sugar is least. The relationshipin these animals varies between 2.x6 and 3.05 and accordingly showsa fairly constant value. It must, however, be emphasized that it isnot always easy to fix exactly the blood sugar level which is reachedafter an injection and this is especially so with regard to the galactose-experiments where it has not been possible to take so frequent blood</p></li><li><p>192 SVEIN LUNDE SVEI~SSO~</p><p>EXI? lIeGLLle.</p><p>EXP'8BGI.oc.</p><p>J 5 MIN.</p><p>\.~</p><p>o</p><p>0 2 3 'f 5 MIN.</p><p>EX? 128.~ GWc.</p><p>0 of 2 J 't tiMIN.</p><p>.....'-----. EXf!138eeoc.XP.13A</p><p>&amp;ALACT.</p><p>[XP3:~ G-Wc.</p><p>0 I 3 5 , MIN.</p><p>[XPIIA</p><p>.:~.of 2 3 't 5 bMIN.</p><p>EX!! 12AGAL ACT.</p><p>..-.</p><p>0 of 3 't 5 , MIN.</p><p>o 1 Z 3 t sMIN.</p><p>Diagrams illustrating some of the experiments reported in the table. Intravenousinjection of a mg sugar per kg body weight at the point of time o. Blood sugar</p><p>level before injection = B1 and blood sugar level after injection = B2B2-B1 = rise in blood sugar</p><p>analyses. The errors which may occur for this reason will not, however,be very great.</p><p>As mentioned above few experiments of this nature have beenrecorded. Corley (1927) has, however, for another purpose injectedrabbits with known quantities of galactose, and has estimated thesugar content in the blood before and also two minutes after the injec-</p></li><li><p>RELATIO:"I BETWEEN BLOOD SUGAR AND TISSUE SUGAR 193</p><p>tion. Reckoned on this single analysis two minutes after the injectionthe relationship between the quantity of galactose injected and theincrease in the blood sugar will be found to be considerably greaterthan in the authors own experiments, ranging, as they do, from 4 to 6.lt is, however, possible to explain this difference between two groupsof animals of the same kind. The calculation of the rise in blood sugarin relation to the total body weight is not an ideal method. Large partsof the body weight are of little or no importance with regard to thedistribution of the injected sugar. These include the fur, fatty tissueand the considerable content of the alimentary tract which can makeup a different percentage of the total weight of various groups of thesame kind of animal, dependent among other things upon the treatmentthey have received.</p><p>I t appears from the experiments performed that in a group ofsimilarly treated animals of the same kind (rabbits) a fairly definiterelation exists between the amount of sugar intravenously injected(reckoned per kg of body weight) and the subsequent rise in the blood</p><p>. increase in tissue sugar .sugar. The quotient seems to be fairly constant.</p><p>increase in blood sugarThe question arises whether we can make the converse statement thata certain increase in the blood sugar corresponds to some degree to adefinite increase in the total content of sugar in the organism. Such astatement seems not illogical if the distribution of glucose in the organismproceeds in accordance with osmotic laws.</p><p>SummaryAn attempt is made to determine the extent of the variations</p><p>taking place in the total content of sugar in the organism when thesugar content in the blood varies. The mode of procedure has beento investigate whether a fairly definite relation exists between theamount of glucose injected reckoned per kg body weight and the risein blood sugar taking place. For a group of similarly treated rabbitsthis relation is found to vary between 2 and 3, the amount of glucoseinjected reckoned per kg body weight being expressed in mg and therise in blood sugar in mg per cent. It is considered possible to use thesefigures for a statement in the reverse direction concerning these particu-lar animals, namely from the rise in blood sugar observed to the increasetaking place in the total content of sugar in the organism.</p></li><li><p>194 SVEIN LUNDE SVEINSSON, RELATION BETWEEN BLOOD SUGAR ETC.</p><p>References</p><p>Burn, I. H. and H. H. Dale, J. Plzysiol. 1924. 59. 164.Cori, c. F., Plzysiol. Rev. 1931. 11. 143.Cori, C. F. and H ..L. Goltz, Proc . Soc. expo Bioi. ,Y. Y. 1925-26. 23. 124.Corley, R. C., J. BioI. Chem. 1927.74. I.Larsson, P. A. and S. L. Sv e i n s s o n , This Archiv 1939. 83. 58.Sveinsson, S. L., Ibidem 1936. 73. 211.</p></li></ul>

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