Idea Transcript
THE
RATE
OF ABSORPTION INTESTINAL
BY EATON (From
the Scripps (Received
M.
OF GLUCOSE TRACT
MACKAY Metabolic for
AND
Clinic,
publication,
H.
THE
C. BERGMAN
La Jolla, March
FROM
California)
8, 1933)
Methods The method used was essentially the same as that of Cori (1). A known amount of glucose solution was introduced into the 453
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Using an obvious but none the less ingenious method, Cori (1) examined the rate of absorption of glucose and other sugars from the intestinal tract and came to the conclusion that the absorption of hexoses is independent of the absolute amount and concentration of sugar in the intestine, giving a straight line relationship between the absorption rate and time. In a study of the rate of absorption of glucose in relation to the diet stated in a previous paper (2) in which the method devised by Cori was used we found no such straight line absorption but instead a marked falling off in the absorption rate during the successive hours after glucose administration. Pierce, Osgood, and Polansky (3) obtained results which led them to conclude that the percentage of glucose absorbed appeared to be dependent upon the amount of glucose remaining unabsorbed in the alimentary tract. Cori et al. (4) explain the findings of these investigators upon the basis that sufficient glucose was not fed to allow the absorption rate to continue at the initial level. Burget, Moore, and Lloyd (5) using Cori’s method found that the rate at which glucose is absorbed decreases with time, a finding in agreement with their results with the isolated ileum loop in the dog. It is unfortunate that their results for the rat are not presented in more detail. The failure of subsequent investigators to confirm the conclusions reached by Cori (1) have made it desirable to reexamine the absorption of glucose from the intestinal tract.
454
Absorption
of Glucose
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stomach of each of a reasonably homogeneous group of fasted albino rats and at various periods thereafter groups of the rats were killed and the amount of glucose remaining in the gastrointestinal tract determined. This, then, gave the average rate of absorption for the group. Since it is a group figure which is being obtained, it is essential that the group be as homogeneous as possible. In a given experiment all of the rats were of the same sex and born within a period of 20 days. The body weight distribution was made as even as possible throughout the group. In certain other details our procedure was slightly different from that used by Cori. Our rats were fasted but allowed water for 40 hours. We chose to give each rat a definite dose of glucose in relation to its body size. To do this a No. 8 or No. 10 urethral catheter of soft rubber was attached to a 5 ml. burette graduated in 0.02 ml. intervals. At the top of the burette a small Luer syringe was inserted in a rubber stopper which closed the burette and served to apply air pressure to the solution. The burette and catheter were filled with the sugar solution, care being taken to exclude air bubbles from the catheter tubing, the tip of the catheter was introduced into the stomach of the rat as described by Cori, and a given amount of sugar solution, as measured by the burette, delivered. We attained a very good accuracy of sugar administration in this manner for variable volumes. When the catheter was withdrawn, it was still filled with solution to the tip. We can confirm Cori in finding that a negligible amount of sugar solution adheres to the outside of the tip. In other respects Cori’s technique was followed. The gastrointestinal tract was removed and treated in the same manner. Glucose was determined by the Somogyi (6) modification of the Shaffer-Hartmann method. Body Size-Cori has assumed that the absorbing surface of the intestine is proportional to the body weight. His data are hardly sufficient for examining this point, for the range of body weights which he examined was only 100 to 180 gm. He chose as his absorption coefficient the amount of substance absorbed per 100 gm. of body weight in 1 hour. Elsewhere (2) we have used as the absorption coeflcient the amount of substance absorbed per 100 sq.cm. of body surface per hour on the basis that it was most reasonable to assume proportionality between the absorbing surface of the intestine and the body surface area (and hence the
E. M. MacKay
and H. C. Bergman
455
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maintenance metabolism) and because we had found that lethal or effective doses of various substances generally bore a more conPierce, Osstant relation to body surface than to body weight. good, and Polansky (3) found a slightly closer relationship between the absorption of glucose and body surface than between its absorption and body weight. Here again the distribution of body weights does not cover a range adequate to give a basis for any general conclusions. To determine the best measure of body size upon which to base the absorption coeficient for glucose, a group of male and female rats of widely varying age and size was given 0.8 cc. (456 mg.) per sq.dm. of body surface of a 57 per cent glucose solution after a fasting period of 40 hours and killed in 1 hour. The data comprise Table I. There is no question but that body surface is the measure of choice as a basis for intestinal absorption. The coefficient of variation of the hourly rate of glucose absorption is smaller when expressed per sq.dm. of body surface than when expressed per 100 gm. of body weight. The coefficient’s are 18.4 on the surface basis and 26.5 on the weight basis. Obviously, determinations of intestinal absorption rat’es are better equalized for differences in the size of the rats by referring them to surface rather than weight. Harris and Benedict (7) in commenting on the same relation between the variability of their basal determinations referred to weight and surface hesitated to ascribe to this relation any significance as a criterion of the relative merits of the two methods of expressing the intensity of basal metabolism. They point out that, from mathematical considerations only, one would expect the surface area of animals of a given species to possess a smaller percentage variability than the body weight. Hence, they argue, the determined basal heat production divided by the body surface will give a less variable series of ratios than will the basal heat production divided by the body weight, and the relation becomes thus a “mathematical necessity” with no physiological significance. A similar view could be taken of the relation of various measurements, such as kidney weight (8) and in the present case glucose absorption from the intestine to body surface. The argument of Mitchell and Carman (9) against the view of Harris and Benedict wit,h a slight substitution of words might be well used here: “The argument of Harris and Benedict fails to
456
Absorption
of Glucose
TABLE
Comparison to Body
of Absorption Coeficients Weight and Body Surface per Sq.Dm. of Body Surface Body
Rat
I
(Mg. per Hour) for Glucose in Relation after a Dose of 456 Mg. of Glucose in 67 Per Cent Concentration
No. Weight
-
Surface
Fed
Gastrointestinal tract
Total
Qm.
sq.cm.
mg.
mg.
my.
258 235 230 218 211 197 196 182 175 168 162 154 135 123 117 113 107 100 92 87 86 86 85 84 82 80 78 77 75 47
459 432 426 411 403 384 383 365 355 345 337 326 299 281 271 265 256 244 232 223 221 221 220 218 214 210 206 204 200 148
2100 1962 1951 1870 1836 1745 1740 1675 1610 1570 1535 1485 688 642 620 608 584 557 528 505 505 511 505 505 516 482 471 470 459 339
1615 1575 1610 1421 1260 1360 1400 1315 1095 1325 1165 1130 403 407 337 417 343 204 285 206 249 214 255 255 286 242 203 210 214 148
485 387 341 449 576 385 340 360 515 245 370 355 285 237 283 191 241 353 243 299 256 297 250 250 230 240 268 260 245 191
Average ............................................. Coefficient of variability .............................
--
absorbed
Per 100 m. body weight
Per 100 8q.cIn. body surface
mg.
mg.
188 165 148 206 273 195 173 198 294 146 228 230 211 193 242 169 225 353 264 343 298 345 294 297 280 300 343 327 327 407 __-
115 89 80 109 144 100 89 99 145 71 110 109 96 84 104 72 94 144 105 134 116 134 113 115 108 114 130 128 123 129
255 26.5
110 18.4
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Glucose
Glucose
E. M. MacKay
and H. C. Bergman
457
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consider one import.ant fact, namely, that the variability of the ratios of [the rate of glucose absorption] to either weight or surface depends not only upon the variability of t,he original [glucose absorption] determinations and of the body surfaces and body weights, but also upon the correlations existing between . . . the [glucose absorption] and the surface. In fact, since [glucose absorption] is so largely determined by size of body, the degree of correlation is the determining factor in the matter. Therefore, the smaller variability of [glucose absorption] per [sq.dm.] of body surface may be fairly interpreted to mean a greater correlation between the two than between [glucose absorption] and the body weight. This greater correlation, may be taken to mean a closer causal relation, certainly of physiological significance.” Henceforth is to be underst’ood as t’he absorption coefficient the amount of the substance under consideration absorbed per unit of time in relat’ion to body surface; e.g., mg. per hour per 100 sq.cm. of body surface in the case of the albino rat. For the determination of body surface we have used the formula of Carman and Mitchell (10). The average absorption coefficient for the rats in Table I receiving 456 mg. of glucose per sq.dm. is 110 mg. per hour. For the females alone it is 109 mg. and the males, 113 mg., an insignificant difference. Recalculating Cori’s figures (l), we find an average for eight rats of 92 mg. This was with variable Wit,h a dose doses averaging 301 mg. per sq.dm. of body surface. of 228 mg. of glucose (Table II) we found an absorption coefficient of 90. In connection with our conclusions in regard to body surface and the absorption coefficient it could be argued that our variability was less in relation to body surface because our dose of glucose was proportional t’o body surface. An indirect argument opposed to this idea is the observation of Orr-Ewing (11) that consistent glucose tolerance tests are obtained in animals of widely different weight only if the dose is adjusted to the body surface. Rate of Absorption-Thirty male rats were each given 0.4 cc. of a 57.02 per cent glucose solution per 100 sq.cm. of body surface and six of these were killed every hour thereafter for 5 hours. This dose of 228 mg. of glucose per sq.dm. of body surface gave (Table II) a gradually falling rate of absorption. At the initial rate of absorption (90 mg. per hour per sq.dm.) sufficient glucose
458
Absorption
of Glucose
TABLE
II Glucose absorbed per 100 sq.cm.
GlUCOK?
absorbed per 100 sq.cm.
AVMage body mxface
Ab;zmpt&n
“;;v;pperiod
Average
Averrtge body surface
Alm;p-
per hr.
period
Average
Glucose absorbed per 100 sq.cm.
AVIS age body surface
Ah&pperiod
per hr.
Avcrage Per hr.
Experixxpt Dose,
1-A
Experignt
1-B
Experi.mnt
l-C*
mg.. hrs.
sq.cm.
m&7.
mg.
sq.cm.
m7.
mg.
s*.cm.
w.
WI.
1 2 3 4 5
419 419 419 419 419
90 168 146 228 230
90 84 73
419 419 419 419 418
101 156 234 296 365
101 78 78 74 73
419 425 421 432 418
138 182 249 292 390
138 91 83 73 78
Experiment after
2. Effect of repeated administration of glucose. a dose of 171 mg. of glucose per sq. dm. body surface mg. per hr. thereafter. Four rats in each group
1 2 3 4 5 Experiment 3. in different
493 491 495 495 496
81 132 231 316 350
81 66 77 79 70
Data for absorption concentrations. Experiment
Concentration, per cent.. Dose, mg..
3-A
coefficients Each figure Experiment
24.75 374
1 2 3 4 5
353 352 352 351 353
* Averages
for four
97 148 216 272 325 rats
Male rats and 57
of female rats after glucose is an average of six rats 3-B
Experiment
58.20 465
97 74 72 68
in each
352 351 351 350 351 group.
109 168 261 300 345
3-C
73.30 442
109 84 87 75 69
352 351 351 350 351
128 196 252 312 385
128 98 84 78 77
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Experiment 1. Data for absorption coefficients of male rats after different amounts of glucose in a concentration of 57.02 per cent. Dose of glucose, mg. per 100 sq. cm. body surface. Each figure unless noted is an average of six rats
E. M. MacKay
and H. C. Bergman
459
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was given to maintain this rate for 2.5 hours. It actually fell during the 2nd hour so that calculation of the average figure for the last hour of each period (90 mg. the 1st hour, 78 mg. the 2nd hour, 53 mg. the 3rd hour, 8 mg. the 4th hour, and 0 mg. the last hour) even indicated some absorption of glucose in the 4th hour. This calculation involves considerable error, but it is interesting that the total amount of glucose found to be absorbed over the 4 hours is 229 mg. and 228 mg. were fed. In an attempt to prevent the falling off of the absorption rate an experiment was carried out (Table II, Experiment 2) in which the glucose in the intestine was replenished at the end of each hour. Both the initial dose of glucose and the replacement doses were half of what had been intended but the absorption period averages were better maintained than in any of the other experiments whatever the dose of sugar given. This suggests that the failure of the rate of a.bsorption to be maintained in the preceding experiment was probably due to the decreasing quantity of glucose in the intestine. The influence of varying the amount of glucose administered on the absorption rate has been examined in the first three experiments summarized in Table II. The highest dose caused a diarrhea in a third of the animals and they were discarded. During the 1st hour of absorption, there is a relation between the dose and the rate. After this except for the smallest dose absorption is not particularly related to the dose. Calculated for the last hour of each period (Experiment l-B, 101, 50, 80, 58, and 76 mg. respectively; Experiment l-C, 138, 43, 69, 44, and 99 mg. respectively) the rate is irregular and unrelated to the dose. This may be entirely due to the large error which must enter this calculation but is possibly in part due to the osmotic disturbance produced by the large quantities of hypertonic sugar solution, reaching its maximum in the rats with diarrhea and associated with the entry of water into the intestine as described by Cori (1). One part of the irregular calculat.ed last hour absorption rates after the 1st hour on the two higher doses may have some significance, for in both experiments the absorption rate fell to its lowest level during the 2nd hour, rose again during the 3rd hour, fell the 4th hour, and rose during the 5th hour after sugar was given. To a lesser extent similar changes were found in other experiments (Table II, Experiments 3-B and 3-C).
460
Absorption
of Glucose
DISCUSSION
Our results are not in agreement with those report,ed by Cori (1). With a 50 per cent glucose solution he found a maintained rate for 3 hours but he fed increasing amounts of glucose. In a later experiment (4) the rate was maintained over 3 hours when each group received essentially the same dose. With an 80 per cent solution, Cori found (1) that the rate of absorption of glucose had a tendency to increase during the 5 hour period. We can find no explanation for our failure to confirm these results. We feel that the most importance should be attached to the absorption coefficient for the 1st hour. Its variability is not significantly greater than when absorption was measured over longer periods. In our hands the variation in the absorption coefficient (coefficient of variability = standard deviation of mean expressed as a percentage of the mean) for groups of twenty-two rats each of approximately the same weight and receiving doses of 442 to 684 mg. per 100 sq. cm. of body surface in each group was 14 per cent the lst, 17 per cent the 2nd, and 12 per cent the 3rd hour. It
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Cori (1) found no difference in the absorption coefficient after 25, 50, and 80 per cent glucose solut’ions, but, the dose given varied with the concentration. We have compared the relative influence of 25, 58, and 73 per cent solutjions on the rate in female rats. It was impractical to give the group given the 25 per cent solution the full volume of solution, so their dose is slightly lower than the other two. All of the doses were of the same magnitude. The average figures (Table II, Experiment 3) show very clea,rly in the 1st hour a relation between the absorption rate a.nd the concentration of glucose given. They both increase together. It is evident but in less degree in the coefficients of t,he other absorption periods. Cori found (1) t(hat t,he concentration of glucose in t’he intestinal t’ract decreased steadily after a dose of strong solution. This may be the cause for the falling off in the rate of absorption even when there is an excessive amount of sugar in the int’estine. In Experiment 1-B male rats received 456 mg. per sq. dm. of body surface in 57 per cent solution and in Experiment 3-B female rats were given 465 mg. in 58.2 per cent solution. The averages give no definite evidence that sex has a significant effect upon the rate of glucose absorption under these special conditions.
E. M. MacKay
and H. C. Bergman
461
SUMMARY
The absorption rate of glucose per unit of time from the intestinal tract of male and female rats of various ages bears a more constant relation to body surface than body weight. The amount of glucose absorbed per unit of body surface per hour of time has been used as the absorption coefficient. The absorption coefficient is raised by increases in either the amount or concentration of glucose administered. Whatever the dose of glucose the rate of absorption as measured by the method used here decreases with time after it is given. Addendum-After this manuscript was submitted for publication, a paper by Trimble, Carey, and Maddock (12) on the rate of absorption of glucose in the dog appeared. Their results are interpreted to show that the rate of absorption is the same for each of the first 3 hours after glucose administration. This is apparently true under their special conditions, but the group in which absorption continued for 1 hour received 2.12 gm., the group in which absorption continued for 2 hours 3.21 pm., and the group in which absorption continued for 3 hours 4.26 gm. of glucose per kilo. This would make the 1st hour of the 3 hour period higher than that of the 2 hour period, which in turn would be higher than the 1 hour period. It is probable that there was a falling off in the absorption rate in both the 2 hour and 3 hour periods but that the increasing doses of glucose led to an apparently sustained average absorption rate. BIBLIOGRAPHY
1. Cori, C. F., J. Biol. Chem., 66, 691 (1925). 2. MacKay, E. M., and Bergman, H. C., J. Nutrition, in press. 3. Pierce, H. B., Osgood, H. S., and Polansky, J. B., J. Nutrition, 1,247 (1928-29). 4. Cori, C. F., Cori, G. T., and Goltz, H. L., Proc. Sot. Exp. Biol. and Med., 24, 433 (1929).
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would seem then that the higher absorption coefficient found in the 1st hour after sugar is given is due not to any error inherent in the method and influencing particularly the 1st hour but to the fact that the rate of absorption decreases after the 1st hour. Our experiments lead us to the conclusion that the true relation of the rate of absorption from the intestine to the amount and concentration of material in the intestine can only be established in experiments in which the stomach contents are considered separately.
Absorption
of Glucose
5. Burget, G. E., Moore, P., and,Lloyd, R., Am. J. Phpsiol., 101,565 (1932). 6. Shaffer, P. A., and Somogyi, M., J. Biol. Chem., 100, 695 (1933). 7. Harris, J. A., and Benedict, F. G., Carnegie Inst. Washington, Pub. No. 279 (1919). 8. MacKay, L. L., and MacKay, E. M., Am. J. Physiol., 83, 191 (1927). 9. Mitchell, H. H., and Carman, G. G., Am. J. Physiol., 76, 385 (1926). 10. Carman, G. G., and Mitchell, H. H., Am. J. Physiol., 76, 380 (1926). 11. Orr-Ewing, J., J. Physiol., ‘73, 365 (1931). 12. Trimble, H. C., Carey, B. W., Jr., and Maddock, S. J., J. BioZ. Chem., 100, 125 (1933).
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THE RATE OF ABSORPTION OF GLUCOSE FROM THE INTESTINAL TRACT Eaton M. MacKay and H. C. Bergman J. Biol. Chem. 1933, 101:453-462.
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