THE ABSORPTIONOF HEXOSESFROMTHE UPPERPART OFTHE SMALL INTESTINE IN MAN

By JUDA GROEN1

(Fromn the Thorntdike Memorial Laboratory, Second anid Foutrth Medical Services (Harvard),Bostont City Hospital, anzd the Departmenit of Medicinie, Harvard Mlledical

School, Bostont)

(Received for publication November 28, 1936)

The most direct approach to the study of ab-sorption fronm the gastro-intestinal tract, both inman and in animals, is offered by those methodsthat make use of the introduction of a knownamount of a test substance into the alimentarycanal, followed by the estimation of what is leftafter a definite period of time. Cori (1, 2),working with animals, introduced the substanceby stomach tube, killed the animal after a certaintime, and determined the amount of the substancestill present in the digestive tract at that moment.His technique has been adopted by many otherphysiologists. The procedure of intestinal intu-bation with the aid of a rubber tube having acollapsible balloon at its lower end developed bvMiller and Abbott (3) offered an opportunity fora direct study of intestinal absorption in man.The present paper gives the results of a study ofthe absorption of three hexoses: glucose, galactoseand levulose in normial adult human subjects.Similar studies, carried out on patients with in-testinal disturbances will be reported elsewhere.

METHODS

A complete description of the tube is given by Millerand Abbott (3) and Owles (4). Their technique hasbeen modified for the present investigation.

Principles. Miller and Abbott have recommended theuse of a three-lumen tube furnished with two balloons forabsorption experiments. They contend that in studyingabsorption in segments of small intestine that are isolatedbetween two balloons an objective measurement of theprocess of absorption per se is obtained. On the otherhand, it seemed to us that under these circumstances afree flow of gastric juice and bile into the segment thatis being studied cannot take place, which might interferewith the normal conditions of absorption. Moreover, inworking with hypertonic solutions a considerable secre-tion of fluid takes place from the intestinal wall into thelumen. The accumulation of fluid tends to distend anisolated loop which may give rise to pain and leakage.

1 Rockefeller Foundation Fellow, 1935-1936.

For these reasons, we have chosen a tube with twolumina and only one balloon.

The tube is furnished with metal markers at certainpoints which enable the investigator to ascertain its exactposition on the x-ray screen or on an x-ray plate. Oneof the lumina leads into the collapsible rubber balloon at-tached at the end of the tube. Once the tip of the tubereaches the jejunum the inflation of the balloon with airto the correct pressure will block off the intestine, somaking the duodenum and upper part of the jejunum acavity closed at the lower end. The second lumen of thetube leads into a number of holes that open above theballoon; through these the test substance is introducedinto the intestine. The test substance is thus in contactwith the mucous membrane of the duodenum and theupper part of the jejunum between the pylorus and theballoon. It is allowed to remain there for a certaintime, after which what is left is recovered by aspirationand washing.

Miller and Abbott (3) observe their subjects underthe fluoroscope during the introduction of the tube. Wehave preferred to introduce the tube first by the routineprocedure customary for intubation of the duodenum.The subject swallows the tube quickly until the 55 cm.mark is reached, when the tip of the tube is in thestomach. The subject then lies down on the right sideand is instructed to continue swallowing the tube slowlyuntil the tip of the tube has reached the desired positioniin the jejunum at about 125 to 130 cm. from the teeth.The time required for the passage of the tip of the tubeto the desired point varies between 2 and 4 hours. Themain delay occurs at the pylorus and the duodeno-jejunalflexure.

The criteria that furnish the indications that the tubehas entered the jejunum are: (1) the length of the tubeswallowed without kinking by the subject; (2) the ap-pearance of bile on aspiration through the tube; (3) thelocalization of the pain experienced by the subj ect oninflation of the balloon. Usually, so long as the balloonis still inside the stomach, the subject feels only a vaguesensation; if the balloon is inside the duodenum, mostsubjects localize the pain on inflation very definitely inthe median epigastric region, a few in the right hypo-chondrium. After the tip of the tube has passed theduodeno-jejunal flexure, the localization becomes muchmore variable: the pain is experienced in the left hypo-chondrium, the umbilical region or the lower part of theabdomen, either to the right or left. Without claimingan absolute validity for these subj ective localizations

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(whiclh can never take the place of an x-ray control), wehave obtained from them very useful information. Thesubject is now examinied either by fluoroscopy or by ex-posure of an x-ray plate. By this means tl-he exact posi-tion of the tube is definitely ascertainied. This simplifica-tion saves the subjects much exposure to radiation and it

observed to pass either backward tlhrough the pylorus orforward past the balloon (Figure 1). We feel confidenittherefore that no regurgitation took place during the ab-sorption tests to be described, provided the subjects werequiet, the amount of fluid introduced not too great, an(dthe pressure in the balloon not too high.

FIG. 1. THE TUBE IN SITU

The barium is seen to occupy the duo(lenium and upper part of the jejunum.

also makes the method available for investigators whohave not the equipmenit necessary for observing subjectscontinuously under the fluoroscope. Moreover, it makesthe intubation applicable to patients who are too ill tostand much handling.

C onitrols. The question of regurgitation into thestomach during the absorption tests required special con-sideration. In two experiments in which barium sulphatewas added to a concenltrated glucose solution, the fluidcould be seen under the fluoroscope Imlovilig up and downand spreadinig out over the whole of the area betweenthe pylorus and the neck of the balloon. No barium was

In every experiment, some of the stomach contents wasaspirated and tested for sugar. If regurgitation had takenplace the experiment was discarded. Leakage downwardwas adequately prevented if the pressure in the balloonwas kept above 25 cm. of water. This has been demon-strated by Miller and Abbott (3), Owles (4) and our-selves by the introductioni into the gut of non-absorbablesubstances such as vital red or ferric ammonium citratethat could be recovered quantitatively by aspiration 30minutes later.

Subjects. After the first tests, the subjects were oftenable to swallow the tube to the desired point entirely by

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themselves. All subjects used for this study were adults,volunteers, varying in age between 18 and 60 years. Oneof the subjects (S) was a woman; the others were men.All were in a healthy state of nutrition. Their weightsvaried from 120 (S) to 175 pounds (M). Two subjects(T and F) were epileptics, but as far as could be ascer-tained by routine physical and chemical examinations,were without any sign of " organic disease." No sig-nificant differences in absorption that could be attributedto differences in age, sex, or weight of the subjects werediscovered. The absorption values in these individualsseemed sufficiently constant within the limits of experi-mental error to exclude the presence of individual pe-culiarities.

Procedure. By preliminary experiments a period suffi-ciently long to permit absorption of several grams ofsugar was determined. The following standard tech-nique was then adopted, in which the time of the absorp-tion and the time required for aspiration and washingout of the solution were kept constant in every experi-ment. The fasting subject was instructed to swallow thetube until the tip of the tube appeared to be in the correctlocation by the criteria described above. An x-ray pic-ture was then made to ascertain the exact position of thetip inside the intestine and to determine the distance be-tween the pylorus and the neck of the balloon. Thislength was measured from the position inside the in-testine of the metal markers on the tube. Since, as willbe shown later, the absorption rate varies in direct pro-portion with the length of intestinal surface area exposed(Table II), all our experiments, when other variableswere being studied, were carried out with a constantlength (50 cm.) of this " absorption area." Whenever itwas not possible to adjust the tube to just this length acorrection was used in the calculation of the final results.After x-ray control had given evidence that the tubewas in the desired position, the balloon was inflated withair to a pressure of 25 to 40 cm. of water and the mainte-nance of this pressure controlled. The subject was in-structed to lie quietly and avoid coughing.

One hundred cc. of sugar solution were then introducedslowly under constant control of the pressure in theballoon, followed by about 15 cc. of water to force thesolution from the dead space in the tube down into thegut. The introduction of the solution took about 5 min-utes. All this time the pressure in the balloon waswatched and, if necessary, readjusted to the level of 25to 40 cm. of water.

Exactly half an hour after the beginning of the injec-tion of the solution, the intestinal content was aspiratedwith an ordinary syringe. The period between introduc-tion and aspiration will be referred to as " absorptiontime." Aspiration took about 5 minutes, after which athorough washing followed to insure complete recoveryof the material introduced. The washing was carried outby making the subject drink 100 cc. of water four timesat 5-minute intervals. This fluid could usually be aspir-ated from the jejunum 6 to 12 minutes after it had beenswallowed. On its way downward it washed out the re-

maining sugar solution. Half an hour after the firstwithdrawal of the solution from the intestine, Benedict'stest for the presence of sugar in the washings was in-variably negative. At that time the balloon was deflatedand the tube carefully withdrawn.

Intestinal contents and subsequent washings were col-lected separately and analyzed for sugar both by polar-imetry (after precipitation with lead acetate) and by areduction method (Benedict's). Usually the resultsagreed within fairly narrow limits. Chlorides, if de-sired, were determined by Whitehorn's method (5). Inmany experiments a capillary blood sugar curve was de-termined along with the absorption test, using the micromethod of Folin (6).

RESULTS

Influence of concentration on absorption rateof glucose. In this series of 11 experiments thelength of " absorption area " (that is, the dis-tance from the pylorus to the neck of the balloon)was 50 cm. in all tests. The " absorption time "was half an hour. The washing out of the sugarsolution also took half an hour. The quantity ofsolution introduced was always 100 cc. The onlyvariable in the series was therefore the concentra-tion, respectively 5, 7.5, 10, 15, and 20 per cent ofglucose. The results are given in Table I. In the

TABLE I

Influence of concentration on the absorption of glucose by astandard area of 50 cm. length of upper small intestine

Quantity of glucoseSubject Date

Introduced Absorbed

grams grams

M March 16, 1936 5.0 4.50M March 5,1936 7.5 6.17

M November 16, 1935 10.0 7.77E April 15, 1935 10.0 9.00M November 18, 1935 15.0 8.30M December 20, 1935 15.0 7.16M December 23, 1935 15.0 7.00M December 28, 1935 15.0 7.85M November 9, 1935 20.0 7.30S December 5, 1935 20.0 8.50E November 29, 1935 20.0 7.03

Average of 9 experiments 10 to 20 7.77

first two experiments in which the concentrationwas relatively low, there was a definite increasein the rate of absorption with the concentration.However, in 9 experiments in which the concen-tration was 10 per cent or over, the quantity ofglucose absorbed was independent of the amount

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JUDA GROEN

introduced. Apparently the intestine absorbsthese concentrated solutions at a uniform rateabove which no increase is possible. Under theseconditions the amount of glucose absorbed froman area of upper intestine between the pylorusand a point 50 cm. lower down varied from 7.03to 9.0 grams in the 9 experiments recorded here.The average was 7.77 grams.

In comparing these figures with those obtainedby other workers, it should be borne in mind thatalthough the so-called " absorption time " in theseexperiments was one-half hour, the actual timeavailable for absorption was longer, as some ab-sorption must have gone on during the time whenthe glucose solution was being washed out. Thusfrom these observations an idea of the actualamount of glucose absorbed per unit of time canonly be derived by approximation. Usually after40 to 45 minutes the greater part of the sugarsolution had been recovered from the intestine.Assuming that all absorption had taken place bythat time, one may then estimate that the absorp-tion of glucose from a concentrated solution in aloop of human upper intestine of 50 cm. lengthgoes on at a rate of 7.77 grams per 40 to 45 min-utes or 10.36 to 11.65 grams per hour.

TABLE II

Influence of absorption area on absorption of glucose

Length Quantity ofof ab- glucose AbsorptionSub- Date sorp- calculated

jetct tion per 50 cm.araIntro- Ab- length

cm. grams grams gramsS November 26, 1935 if30 10 5.40 9.00S December 2, 1935 40 15 7.00 8.40T March 12, 1936 i45 15 7.73 8.66M Average of 4 i50 15 7.71 7.71

experimentsF March 8, 1936 * 55 15 9.35 8.50E April 30, 1936ft60 15 9.29 7.74E December 13, 1935 *70 15 10.20 7.30

Average for 6 subjects... . , 8.18

Length of absorption area. Table II showsthe results of a second series of 9 experimentsin which absorption time and the quantity of glu-cose introduced (15 grams) being kept constant,the only variable was the length of duodenumand jejunum that took part in the absorption.In these experiments the length of the absorp-

tion area varied from 40 cm. to 70 cm. In oneother experiment, 10 grams of glucose was ad-mitted to a length of 30 cm. of intestine. Theresults show within the limits of the experimentalerror a direct proportional relationship betweenthe length of intestine that takes part in the ab-sorption and the quantity of glucose absorbed.If the results are calculated for a standard ab-sorption area of 50 cm. they fall within the limitsof variation shown in Table I. The minimumabsorption calculated in this way was 7.30 grams,the maximum 9.00 grams, the average value 8.18grams.

TABLE III

Influence of pH on absorption of glucose

Quantity of glucoseSub- Date -____ pHject (calculated)

Introduced Absorbed

grams gramsM Average of 4 15 7.71 7

experiments

M March 3, 1936 15 6.86 12E March 4, 1936 15 6.03 12M March 2, 1936 15 6.79 2M April 22, 1936 15 6.17 2

Influence of pH. Table III shows the resultsof a third series of 4 experiments upon the in-fluence of the pH upon the absorption of glucose.All conditions were the same as in the first seriesof experiments but for the addition of 10 cc. ofN/10 normal NaOHor of 10 cc. N/10 normalHCI to 100 cc. of the 15 per cent glucose solution.The results show that in each case the absorptionof the glucose solution was somewhat diminishedby altering the reaction away from the neutralpoint. At pH 12 the absorption values were 6.03and 6.86, respectively, at pH 2, 6.17 and 6.79,compared with the average of 7.71 for controlexperiments at neutral reaction.

The capacity of the duodenum to buffer its con-tent to a neutral reaction was well brought outby these observations. The fasting content ofthe upper part of the intestine has a neutral reac-tion (pH 7.0 to 7.1). The intestinal contentsaspirated after half an hour were also neutral,irrespective of whether acid or alkaline glucosesolutions had been introduced.

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on absorption of

Quantity ofglucose

Sub- Date Remarksject

Intro- Ab-duced sorbed

grams gramsM November 10, 1935 15 8.30 Vegetarian diet for several

yearsM December 28, 1935 15 7.85 After 14 days on mixed diet

E December 13, 1935 15 7.30 Mixed dietE April 26, 1935 15 7.34 After 4 days on ketogenic

dietE April 30, 1935 15 7.74 After 8 days on ketogenic

diet

T March 12, 1936 15 8.66 After 2 days' starvation

F August 15, 1936 15 8.50 Mixed dietF August 19, 1936 15 9.36 After 4 days' starvationF August 29, 1936 15 8.10 After 10 days of diet low in

carbohydrate and rich infat and protein

Influence of preceding diet and of starvation.Table IV summarizes the results of a fourth se-

ries of 9 experiments undertaken to investigatethe possible influence of the nutritional conditionof the subject on the absorption rate of the glu-cose solution. The amount of glucose introducedwas always 15 grams in 100 cc. of water, the ab-sorption length 50 cm., the absorption and wash-ing time thirty minutes each. Under these cir-cumstances it appeared that the absorption was

essentially the same whether the subjects followeda vegetarian regimen or had taken a diet rich inanimal protein and fat. One of the subjects (E)took a ketogenic diet that contained 25 grams ofcarbohydrate for 8 days, after which time theurine gave a positive reaction for acetone. Theabsorption test gave a normal result.

The effect of complete starvation was testedon two epileptic subjects (T and F). Patient Tstarved for 48 hours, and Patient F for 96 hours.The fluid intake during the starvation was notrestricted. Both showed a high normal absorp-tion for glucose after this period.

Nature of sugar. The effect of the nature ofthe sugar upon the absorption under standardconditions was next investigated. Table V con-

tains the results of a fifth series of 8 experimentsin which galactose solutions of various strengthwere tested. The conditions of the experimentswere the same as for those on glucose absorption.The figures in Table V show that above a con-

centration of 15 per cent the absorption rate is

TABLE V

Quantities of galatose absorbed by a 50 cm. length of uppersmall intestine

Quantity of galactoseSubject Date

Introduced Absorbed

grams gramsM November25, 1935 15 9.95M November 29, 1935 15 10.66E December 31, 1935 15 8.19S December 10, 1935 15 9.61N February 10, 1936 15 11.00G February 14, 1936 15 8.62M December 3, 1935 20 8.70S December 17, 1935 20 8.88

Average .... 15 to 20 9.45

independent of the concentration. The actualamount of galactose absorbed appeared to belarger in the same unit of time than that of glu-cose, the average value being 9.45 grams, varyingfrom a minimum of 8.19 to a maximum of 11.0under the standard conditions. An approxima-tion of the absorption per unit of time based onthe same principles as used above for glucosewould lead to an estimate of 12.60 to 14.17 gramsper hour as the rate of absorption of galactosefrom a concentrated solution in a loop of intestineof 50 cm. length.

TABLE VI

Quantities of levulose absorbed by a 50 cm. length of uppersmall intestine

Quantity of levuloseSubject Date

Introduced Absorbed

grams gramsM December 24, 1935 6 4.86E January 8, 1936 7 5.77M December 16, 1935 8 5.46S January 13, 1936 8 4.37M December 11, 1935 10 4.74S January 21, 1936 10 5.42E January 22, 1936 10 5.79

Average ... 6 to 10 5.20

Table VI shows the results of a sixth series of7 experiments upon the absorption of levulose.The absorption rate appears to be constant forsolutions above 6 per cent in concentration. Theabsorption of levulose is definitely slower thanthat of glucose or galactose, varying from 4.37 to5.79 grams under standard conditions. The av-

TABLE IV

Influence of preceding dietary regimenglucose

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JUDA GROEN

erage value was 5.20 grams. Approximationwould yield an absorption rate of 6.93 to 7.80grams of levulose per hour from a 50 cm. lengthof intestine.

It will be noted that the maximum absorptionrate in the case of levulose occurred at a lowerconcentration (6 per cent) than that of glucose(10 per cent). Apparently the critical levelabove which the absorption rate becomes uniformis not determined by the osmotic concentrationand may be a characteristic property of every in-dividual sugar.

Influence of the absorption time. In a seventhseries of 4 experiments, all carried out with galac-tose on the same subject, the " absorption time "was varied to respectively, 0, 15, 30, and 45 min-utes with otherwise standard conditions. Thewashing time was kept constant at one-half hourin all instances. The results are shown in TableVII. As could be expected, a direct, almost

TABLE VII

Influence of "absorption time" upon absorption ofgalactose

Quantity ofgalactose Absorp-

Subject Date tionIntro- Ab- timeduced sorbed

grams grams minutesE March 11, 1936 15 2.41 0E February 19, 1936 15 5.73 15E December 31, 1935 15 8.19 30E December 18, 1935 15 13.00 45

linear relationship was found between the quan-

tity absorbed and the time allowed for absorption.In the experiment in which the absorption timewas " zero," the aspiration of the solution was

started immediately after it had been introduced.All the absorption that took place must have oc-

curred, therefore, during the injection of thesolution (5 minutes) and the "washing time"(30 minutes).

This series of experiments also furnishes datafrom which a more exact idea of the absolutevalue for the absorption rate of galactose can beobtained. By deducting the figure for " 0 " min-ute absorption time from that for the 15-minuteperiod, etc., values for the quantity absorbedduring exactly 15 and 30 minutes can be ob-tained. These values vary from 2.46 to 4.81

grams, with an average of 3.44 grams per 15minutes or 13.76 grams per hour. This agreesfairly well with the values of 12.60 to 14.17 thathave been arrived at by approximation.

Osmotic relationships. The quantity of fluidrecovered one-half hour after the introduction of100 cc. of the concentrated sugar solution intothe intestine was always larger than the amountintroduced and varied between 140 and 250 cc.,with an average of 200 cc. Apparently, whilesugar was being absorbed, fluid had moved intothe lumen of the intestine. Though in part prob-ably derived from the small intestinal wall, bile,pancreatic juice, and gastric juice may haveflowed into the intestine and contributed to thedilution of the test solution. During the nexthalf hour, while the subjects were drinking atotal of 400 cc. of water, another volume of fluidwas collected. The washings varied in volumefrom 200 to 400 cc., dependent on the amount ofwater that was retained inside the stomach.

The concentration of glucose found in the in-testinal contents after half an hour varied from2.11 to 3.24 grams per 100 cc., with an averageof 2.50 per cent. The concentration of glucosewas apparently reduced to about half its isotonicconcentration (5.4 per cent). This may seemstrange at first, as one would not expect a dilutionbelow isotonicity. It should be remembered,however, that the normal duodeno-jejunal juicecontains chloride in almost the same concentrationas the blood plasma (in our experience between279 and 475 mgm. per 100 cc.; according to Karrand Abbott (7) between 178 and 528 mgm. per100 cc.). The chlorides, together with the bi-carbonate, maintain the normal osmotic pressureof the intestinal juice. The dilution of a hyper-tonic glucose solution inside the intestine will goon, therefore, until the concentration of glucoseplus the concentration of the other constituentstogether make up isotonicity. That this holdstrue was brought out by determination of thechloride in the intestinal content. In the fluidaspirated one-half hour after the introduction ofthe glucose solution, the chloride concentrationwas markedly lower than before the introductionof the glucose. The values varied between 212and 287 mgm. per 100 cc. (Table VIII). More-over, there was an almost complete inversely pro-portional relationship between the glucose and

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ABSORPTIONOF HEXOSESIN MAN

TABLE VIII

Concentration of glucose and chloride in intestinal content30 minutes after introduction of 100 cc. 15 per cent

glucose solution

Sub- Date Glucose Chlorideject

1986 grams per mgm. per100 cc. 100 cc.

E September 29 3.24 212F April 23 3.14 2190 September 25 2.57 229E April 27 2.52 224M May 19 2.48 228E April 30 2.26 229S April 28 2.26 243F August 19 2.22 287F August 14 2.14 287F May 12 2.11 271

Average .2.49 243

chloride concentration, chlorides being higher inthe fluids with the lower glucose content.

If we express both glucose and chloride con-centration in milliequivalents and assume that allthe cations present are monovalent, we can calcu-late the sum of the osmotic concentrations ofglucose, the chlorides and the cations together.For this purpose we simply multiply the chlorideconcentration by 2, and add this to the glucoseconcentration. Table IX shows the figures ob-

TABLE IX

Glucose and chloride concentration and their combinedosmotic pressure in intestinal content at end of

absorption period

Glucse hloideCombined osmoticSub- Date conc~en chonden pressure of glucose,ject traateticoncen- concen- chlorides and theirject tration tration ~monovalent cations

1986 m.eq. per m.eq. per "miUiosmoles" per100 cc. 100 cc. 100 cc.

E September 29 18.00 5.99 29.98F April 23 17.45 6.16 29.770 September 25 14.28 6.45 27.18E April 27 14.00 6.31 26.62M May 19 13.78 6.42 26.60E April 30 12.56 6.46 25.48S April 28 12.56 6.85 26.26F August 19 12.34 8.09 28.52F August 14 11.89 8.09 28.07F May 12 11.72 7.64 27.00

Average . 13.86 6.84 27.55

tained in this manner. The calculated osmoticpressure in this table is expressed as "millios-moles " per 100 cc. There is some variation inthe figures but on the whole the total concentrationof glucose, plus chloride, plus cation, seems to be

fairly constant, varying between 25.48 and 29.77,with an average of 27.29 milliosmoles per 100 cc.Wedo not know how much carbonate was pres-ent in the intestinal content, but this can onlyhave been of small importance (Karr and Abbott(7)). If we compare our calculated osmoticconcentration with the normal osmotic concentra-tion of blood plasma (which is about 30 millios-moles per 100 cc.) it may be safely concludedthat half an hour after the introduction of aconcentrated solution of glucose the human smallintestine has reestablished osmotic equilibrium be-tween its content and the blood plasma.

Blood sugar curves. In a number of testscapillary blood sugar values were determinedwhile glucose, galactose, or levulose was being ab-sorbed. Not all the values obtained will be givenhere. Table X shows only the maximum, min-

TABLE X

Blood sugar values in milligrams per 100 cc. during theabsorption of hexose from the upper part of the

small intestine

Time after introduction of 100 cc. ofsolution

Sgr Blood Fast-Sugar sugar inghour hour hour hour hours hours

Glucose Highest 119 153 161 173 188 125 117(11 Lowest 99 101 115 118 102 112 108curves) Average 107 122 131 134 127 117 111

Galactose Highest 118 151 152 154 151 125 120(7 Lowest 105 108 115 110 101 109 104curves) Average 108 120 132 130 122 117 108

Levulose Highest 112 117 125 121 116 118 107(5 Lowest 101 105 109 106 103 100 100curves) Average 106 113 114 112 110 107 103

imum, and average values that were found fast-ing and at successive intervals of one-quarterhour after the introduction of the sugar solution.

(a) Glucose. In almost all instances whenglucose was given the blood sugar showed a defi-nite rise after one-quarter hour, reached a peakafter one-half, three-quarters or one hour, thendropped rather steeply and reached its originalvalue again after between one and one-half andone and three-quarter hours. The height of thepeak varied between 119 mgm. per 100 cc., and188 mgm. per 100 cc. The highest point of theaverage curve was 134 mgm. per 100 cc. afterthree-quarters of an hour. There was no definite

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JUDA GROEN

relationship between the amount of glucose in-troduced and the height to which the blood sugarrose. It is noteworthy that although the with-drawal of the glucose solution from the intestinewas started after one-half hour, the blood sugarlevel in many instances continued to rise anddropped only after one hour. Glycosuria duringthe test did not occur in any instance.

(b) Galactose. The blood sugar curves afteradministration of galactose through the tube didnot differ materially from those when glucose wasbeing absorbed. Apparently, although the ab-sorption rate of galactose is greater than that ofglucose the storage mechanism of the body takescare of the quantity absorbed under the condi-tions of our experiment. A slight galactosuriaoccurred in five instances.

(c) Levulose. The " glycemic " effect of thissugar was decidedly less than that of glucose orgalactose. The highest blood sugar value ob-tained with levulose was only 125 mgm. per 100cc. (expressed as glucose). Whether this smallerrise is caused by the slower absorption rate onlyor whether the tissues remove levulose from theblood at a higher speed than the other sugarscannot be decided here. No levulose appearedin the urine of any of the subjects.

DISCUSSION

The present status of our knowledge of theabsorption of carbohydrates has been reviewedrecently by Pierce (8). Only those points bear-ing directly on the results obtained in this studyneed therefore be discussed here.

The fundamental work of Cori (1) carriedout in rats has definitely established that the ab-sorption of a simple sugar from the intestinaltract is independent of the quantity of sugar pres-ent in the alimentary canal. It should be remem-bered, however, that this "law" was found byintroducing concentrated solutions into the ani-mals. The validity of Cori's law has been con-firmed by Cori, Cori and Goltz (9), Holtz andSchreiber (10), Magee (11), Trimble, Carey andMaddock (12), and Verzar (13). Trimble andMaddock (14), working with dogs, made the im-portant observation that Cori's law also applieswhen the glucose solution is introduced directlyinto the duodenum. Other investigators (15, 16)

failed to confirm Cori's observations in detail buttheir results are in substantial agreement with hisfindings. There still exists some disagreementbetween investigators whether the absorption rateshould best be expressed per unit of intestinalsurface (16) or per kilogram of body weight(1, 12).

Our own results confirm Cori's law for the ab-sorption of concentrated sugar solutions from thehuman small intestine. The results did not war-rant a calculation of the absorption rate per kilo-gram body weight. The area of intestine exposedto the sugar solution appeared to be of para-mount importance for the amount of sugar ab-sorbed. The absorption rate per unit of time wasconstant for a given intestinal length which wasassumed to be a relative measure of the surfacearea.

The absorption of comparatively dilute sugarsolutions has been studied in animals by Nagano(17), Hewitt (18), and London and Polowzowa(19), who found that the absorption rate in-creased with the concentration. Abbott, Karrand Miller (20) have shown this to be equallytrue for the human small intestine. The few ex-periments undertaken by us with glucose solutionsof low concentrations (Table I) confirm their ob-servations. This does not contradict the workof Cori on the absorption of concentrated solu-tions. Our results brought out very definitelythat above a certain concentration, which seemsto be different for various sugars, the absorptionproceeds at a uniform rate.

London and Polowzowa (19), and Magee andReid (21), both working with dogs, found thata maximum absorption rate for glucose estab-lished itself at concentrations of 11.5 and 13 percent, respectively. In our experiments the ab-sorption rate became maximal at concentrationsof 10 per cent or over.

The literature contains a few conflicting reportson the influence of the pH on the absorption rateof glucose (22, 23). From our data we cannotoffer an adequate explanation for the slowingdown of the absorption rate by the addition ofacid or alkali to the glucose solution, as observedby us. The effect need not be specific but mightbe caused solely by the increase in osmotic con-centration of the intestinal content (24). Ap-parently a neutral reaction affords optimum con-

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ditions for the absorption of glucose in the intes-tine, but this does not necessarily hold true forother substances. It appears that the intestinepossesses an efficient mechanism for the protec-tion of the reaction of its content, a point whichhas been extensively studied by Karr and Abbott(7) and Stevens (25).

Various workers have shown that the intestineabsorbs different sugars at a different rate. Ac-cording to Cori, the proportion of the averageabsorption rates of galactose, glucose, and levu-lose (glucose being taken as 100) in the rat canbe expressed as 110: 100: 43. Our results yieldfor this relationship 122: 100: 67, which, consid-ering the experimental error in both animal andhuman experiments, may be called a satisfactoryagreement. Cori (1, 2), Wildbrandt and Laszt(26), Verzar (13), and Westenbrink (27) haverightly concluded that since every sugar has itsindividual absorption rate the process of absorp-tion in the intestine, even of such simple com-pounds, cannot be a purely diffusion phenomenon,but must be an active cellular process inside theepithelium of the gut. Whatever the nature ofthis physiological process of sugar absorptionmay be (28, 29, 30, 31), it appears to be of thesame nature both in animals and in man.

A comparison of the actual absorption rates inanimals and in man seems hardly warranted be-cause of the different way in which the studieshave been conducted. In the animal, the sub-stance is introduced either into the stomach orinto the duodenum and then allowed to spreadout over all the available intestinal area where theperistalsis will carry it. In our experiments theabsorption was limited to a closed loop of in-testine of 50 cm. in length. Even so, it is in-teresting to note that the approximate averageabsorption rates of glucose per hour when calcu-lated per kilogram body weight were:

For the rat .. 2.00 grams (1, 9, 13, 16)2For the dog........... 1.00 gram (14)For the human...........0.18 gram (presentstudy)

This furnishes another example of the higherspeed at which the living processes seem to goon in the smaller animals.

Most of the blood sugar curves obtained inour experiments were only slightly lower thanthose observed in the capillary blood during the

first hour of an ordinary glucose tolerance test,when 50 to 100 grams are given by mouth toa normal individual. We know, however, thatof this large quantity only a limited portion ata time is admitted by the pylorus to the upperpart of the intestine. As all other factors in-fluencing the blood sugar curve seem to be thesame in the oral and intestinal administration ofthe sugar, it may be concluded that even if 50to 100 grams of glucose are given by mouth, theactual absorption is only slightly more than when10 to 20 grams are fed into 50 cm. of the upperpart of the intestine. We have estimated theapproximate rate of absorption in our experi-ments as 10.5 to 12 grams per hour. From thestudy of the rise in blood sugar during this ab-sorption, we would venture to suggest that evenwhen much larger quantities of glucose are givenby mouth the absorption rate is only slightly morethan this figure. This would imply that the timefor the absorption of a glucose test meal of 50grams would be 4 hours or somewhat less. Wehave little doubt that if 50 grams of glucose wereintroduced directly into the whole of the intestinethe absorption would go on at a higher rate andthe blood sugar would rise to higher levels (32).Given by mouth, however, the pylorus takes carethat the absorption does not take place at a higherspeed than the storage mechanism can keep upwith (10).

SUMMARY

The absorption of glucose, galactose, and levu-lose from the upper part of the human small in-testine has been studied by a simplified methodof intestinal intubation. The results show thata given length of the human small intestine dur-ing a constant interval absorbs a constant amountof a simple sugar from a concentrated solution.Under these conditions, the amount of sugar ab-sorbed is independent of the concentration abovea certain level. The amount of sugar absorbedincreases with an increase in intestinal surface.The quantity absorbed is proportional to the timeallowed for absorption. The addition of dilutehydrochloric acid or sodium hydroxide to the glu-cose solution diminishes the amount of sugar ab-sorbed. No influence of the immediately preced-ing diet or of starvation on the absorption ratecould be detected.

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JUDA GROEN

Glucose, galactose, and levulose have their own

individual absorption rates which averaged, underthe conditions of our experiments, 7.77, 9.45, and5.20 grams, respectively, the relation being 100:122: 67. During the absorption the concentratedsugar solution inside the intestine is rapidly di-luted so that after one-half hour the total osmoticconcentration of the intestinal contents equalsthat of the blood plasma.

Blood sugar values during the absorption of theglucose, galactose, and levulose from the intestinewere determined. The curves obtained indicatesimilar effects for glucose and galactose but a lesseffect upon blood sugar for levulose than forglucose.

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