Crider and Mogan [1934] and Werle, Brody, Ligon, Read and Quigley [1941],

Transcription

1 Quarterly Journal of Experimental Phy8iology (1972) 57, THE EFFECT OF GLUCOSE, GALACTOSE AND SORBITOL ON GASTRIC EMPTYING IN THE YOUNG PIG. By J. H. REED* and D. E. KIDDER. From the Department of Veterinary Medicine, University of Bristol, Langford House, Langford, Bristol BS18 7DU. (Received for publication 22nd June 1971) The emptying times of glucose solutions of different concentrations by the stomach of the young pig have been compared. The emptying of glucose solutions has also been compared with that of galactose, sorbitol and sodium chloride of similar osmolarity. The more concentrated the glucose solution, the more slowly it is emptied, as is reported in other species. The emptying rate of galactose is similar to that of glucose and slower than sorbitol which is emptied at a similar rate to sodium chloride. The mechanism of gastric emptying has been studied mainly in man, the dog and the rat. Review articles based on these studies have been written by Thomas [1957] and Hunt and Knox [1968]. The initial stimulus for emptying is the volume of contents in the stomach [Hunt and Macdonald, 1954]. The mechanism, a succession of rhythmic contractions passing down the stomach through the pylorus and along the duodenum, was demonstrated in the dog by Thomas, Crider and Mogan [1934] and Werle, Brody, Ligon, Read and Quigley [1941], and in man by Quigley [1941]. The emptying process has long been known to be inhibited by the presence of food substances in the duodenum, different foods producing different degrees of of inhibition [Marbaix, 1898]. This inhibition is partly nervous [Hunt and Knox, 1964] and partly due to the release into the bloodstream of a hormone [Kosaka, Lim, Ling and Liu, 1932] which Lim [1933] called 'Enterogastrone'. A preparation with enterogastrone activity, that is inhibitory action on gastric motility and emptying, was extracted from dog duodenal mucosa by Kosaka et al. [1932] and from pig duodenal mucosa by Gray, Bradley and Ivy [1937]. A purer preparation with much greater enterogastrone activity and free of secretin, pancreozymin or other known duodenal hormones, has now been obtained by Brown, Mutt and Pederson [1970] from pig duodenum. The isolation of the relevant hormone from pig duodenum, and the intermittent pattern of gastric emptying after a meal found in studies on pigs using duodenal fistulae [Kvasnitskii, 1951; Auffrey, Martinet and R6rat, 1967; Freeman, Noakes, Annison and Hill, 1968] indicates that their emptying process resembles that ofman and the dog. It seemed possible that the pig would prove a suitable experimental animal for studies of the emptying process. Simple sugar solutions which have been shown to produce this inhibitory effect [Quigley and Phelps, 1934; Fenton, 1945, Hunt, 1956 and 1963] were used in order to make the interpretation of results as unambiguous as possible. * Present address: Ontario, Canada. Department of Clinical Studies, University of Guelph, Guelph, 30

2 Monosaccharides and gastric emptying in pig 31 MATERIALS AND METHODS Pigs. Four Large White x Wessex females aged 9-26 weeks were used (Table I) kept from 4 to 5 weeks on a pelleted starter ration (Creep feed, B.O.C.M.) C(annulation. A perspex cannula was placed in the wall of the stomach on the greater curvature opposite the major gastro-splenic vein and exteriorized through the left abdominal wall according to the technique described by Markowitz, Archibald and Downie [1964], care being taken to ensure that the stomach was not stretched into an unnatural position. A week after surgery the pigs were transferred to adjustable metabolism cages and a further two weeks allowed to elapse before experiments were started. In a preliminary experiment on three of the pigs a fluid X-ray contrast medium was infused through the fistula into the stomach and then allowed to drain out. Observation with an image-intensifier and radiographs showed that drainage was complete except for a little of the barium sulphate contrast medium sticking to the walls of the stomach. The emptying test. This consisted of the infusion of 500 ml. of a test solution containing in addition 30 mg/ml. of polyethylene glycol (P.E.G.) M.W (Shell Chemicals) as a marker. At the stated time after infusion the liquid remaining in the stomach was drained out, its volume and P.E.G. concentration measured and the volume of the original solution remaining in the stomach at that time thus calculated. The pig was fasted for 22 hr prior to the morning of the test, but allowed water ad lib. On the morning of the test day, water was removed from the cage and the gastric cannula opened to drain stomach contents. An adaptor was attached to the cannula and a rubber tube with a funnel at the other end attached to the adaptor. The stomach was washed out with tepid water which was removed by lowering the funnel. Two 500 ml. rinses were usually sufficient to remove food particles and mucus, but if four rinses were insufficient the test was abandoned. The final rinse was allowed to drain for 3 min. The test solution warmed to 3700, was then infused through a clean tube over a 1 min period and fluid remaining in the tube forced into the stomach by blowing. The tube was clamped with forceps, the adaptor closed and the delivering tube TABLE I. The number of experiments carried out with each pig with each test soluton for the variou time intervals between infusion of the solution and draining out. (Numbers in parentheses are thosefor the second solution). Conc. No. of tests in each period on Pig Age per eah solution no. (weeks) Substance cent 10 min 20 min 30 min 40 min 60 min Glucose 5, (3) Glucose Glucose 5, Glucose Sorbitol, glucose Sodium chloride Sorbitol, glucose 10 1(2) Glucose, galactose, sorbitol 20 Sorbitol Glucose Galactose, sorbitol Glucose 5, Glucose, galactose, sorbitol 17 Glucose, sorbitol Glucose

3 32 Reed and Kidder removed and any fluid remaining in it measured so as to calculate the exact volume infused into the stomach. The test solution was left in the stomach for the required time and then drained into a flask. Fifty millilitres of water was then run into the stomach and drained, and the tube washed through with 5 ml. of water. The volumes and P.E.G. concentrations of the recovered test solution and washings were measured, and from this the volume ofthe original solution left in the stomach at the time in question was calculated. The pig was given water to drink and at least 45 min allowed to pass before another test was done. No more than three tests were done in any one day, and a day's rest was allowed before a further test was carried out on any pig. Table I lists the experiments done on each pig and the age at which they were done. P.E.G. was determined by the method of Hyd6n [1955]. RESIULTS Different glucose concentrations. Fig. 1 gives the individual results for all the pigs for the emptying of 5 per cent and 35 per cent glucose solutions. Fig. 2 %5000; inn 60 FIG. 1. FIG. 2. LOD ~~~~~~%400 _ ~~~~~~~~~~~35% V ~~~~~~~~~ ,Gluc se 100 io E ZI.-~~~~~~~~ DURATION OF TESTS (MINUTES) DURA1TON OF TESTS (MINUTES) The gastric emptying of 5 and 35 per cent glucose solutions. All the individual results obtained using these concentrations are given. 0 Pig 1, 0 Pig 2, A Pig 3, X Pig 4. Comparison of emptying of 5, 10, 20 and 35 per cent glucose solutions. Each point is the mean of all the pigs compared at these times on the solution concerned (Pigs 2 and 4 with 10 per cent solution and all 4 pigs with 5 and 35 per cent solution). gives the mean results for the emptying of 5, 10, 20 and 35 per cent glucose solutions in those pigs in which 10, 20, 30 and 60 rain intervals had been used (see Table I). In each case emptying is more complete at the end of each of the test periods with the weaker solution. Glucose, sorbitol and sodium chloride. Fig. 3 compares the emptying of 5 per cent glucose with two solutions of similar osmolarity, namely 5 per cent io%

4 Monosaccharides and gastric emptying in pig 33 &V CZ 40 g~~~300 ~ ~ ~ ~ '3~ A * i~~~~~~~~c A~~~~ AE~~~~~~~~~~~~ *U.' C. A o A 00 FIG. 3. FIG. 4. o DURATION OF TESTS (MINUTES) DURATION OF TESTS (MINUTES) Comparison of emptying of 500 ml. of isotonic solutions of sorbitol, glucose and saline. * Glucose, A sorbitol, * saline. Comparison of emptying 500 ml. of 10 per cent solution of glucose and sorbitol. *Glucose, A sorbitol. sorbitol and 0 9 per cent sodium chloride. Fig. 4 shows the emptying with 10 per cent glucose and 10 per cent sorbitol. The sorbitol and sodium chloride show similar rapid emptying while the glucose in each case is emptied far more slowly. TABLE II. The volumes of infused test solution left in the stomach 10, 20, 30 and 40 min after infusion of 500 ml. of 10 per cent glucose, galactose or sorbitol. Each value i8 the mean offour tests with the standard deviation. The values of P are for the comparison of sorbitol with glucose and sorbitol with galactose. Time (min) Glucose Galactose Sorbitol P N.S. ±60 ±24 ± *05 ±30 ±84 ± *05 ± 7 ±57 ± N.S. ±59 ±40 ±89 Glucose, galactose and sorbitol. This comparison was made on two pigs, each time in two different orders, namely glucose, galactose, sorbitol and sorbitol, galactose, glucose. The results are shown in Table II. Analyses of variance for each time interval showed no significant difference between pigs or between orders of administration at any of the time intervals. VOL. LVII, NO. I

5 34 Reed and Kidder These factors were therefore pooled and using Duncan's multiple range test a significant difference was found between sorbitol and glucose, and sorbitol and galactose for the 20 and 30 min time intervals. There were no significant differences between glucose and galactose. Thus the sorbitol again emptied more rapidly than the glucose, while the galactose closely resembled tbe glucose. DISCUSSION The increase in degree of inhibition of gastric emptying by glucose solution when the concentration is progressively increased from 5 per cent to 35 (Figs. 1 and 2) is in agreement with the findings of Fenton [1945] in the rat and Hunt [1956, 1963] in man. The difference between the effects of glucose and sorbitol (Fig. 4 and Table II) differs from Hunt's findings [1956, 1963] in man, where over the range he used, m-osmol/l. ( per cent), glucose and sorbitol produced the same degree of inhibition. It is difficult to say whether the difference between our results and those of Hunt is due to technique (he measured retained volume while we measured retained marker), concentration, in that we used a slightly higher concentration than the highest used by Hunt, or is a species difference. Hunt postulated [Hunt and Pathak, 1960; Hunt and Knox, 1968] that at low osmotic concentrations the osmolarity of the solution is the main factor producing inhibition, but accepted that at higher concentrations glucose must have some other effect related to its chemical composition. Elias, Gibson, Greenwood, Hunt and Tripp [1968] suggested that th-e inhibitory effect of sugars on gastric emptying was initiated by an osmotic effect within the mucosa after the first stage of absorption. This was on the basis of comparisons on human volunteers of the inhibitory effects of glucose, galactose, fructose, mixtures of these sugars and disaccharides containing them. They found disaccharides to have the same action as the same quantity of the constituent monosaccharides, and, of these, glucose had the greatest effect, galactose rather less, and fructose about half that of glucose. This is in approximate agreement with the relative rates of absorption from the intestine [Cori, 1925, Wilson, 1962]. Our results would also fit this hypothesis, as sorbitol, which we found to have little effect on emptying, is transported, at least in vitro, much less rapidly than glucose or galactose [Wilson and Landau, 1960]. The absence of any difference between glucose and galactose in our experiments fits the relative rates of absorption even better than the results of Elias et at. It is not possible to say whether this small difference between our results and theirs is due to species difference or experimental conditions. It would also be possible to postulate on the basis of our results and those of Elias et at. that the inhibitory effect was initiated by the active operation of an absorptive mechanism rather than by the appearance of the absorbate in the mucosal cell. The greater volume of original sorbitol solution found in the stomach after the one hour test than after the 30 min test in several experiments (Figs. 3 and 4) is difficult to explain unless sorbitol solution has a tendency to produce duodenal regurgitation.

6 Monosaccharides and gastric emptying in pig 35 ACKNOWLEDGMENTS Thanks are due to Professor A. Messervy for the use of surgical and radiographic facilities in the department of Veterinary Surgery, and to Professor T. K. Ewer of the department of Animal Husbandry for the use of the metabolic cages, also to Mr M. Parsons and Mr J. Conibear, for the figures and Dr J. Curtis for the statistics. REFERENCES AUFFREY, P., MARTINET, J. and R1ERAT, A. (1967). Quelques aspects du transit gastrointestinal chez le porc. Annales de biologie animale, biochimie et biophysique, 7, BROWN, J. C., MUTT, V. and PEDERSON, R. A. (1970). Further purification of a polypeptide demonstrating enterogastrone activity. Journal of Physiology, 209, CORI, C. F. (1925). The fate of sugar in the animal body. The rate of absorption of hexoses and pentoses from the intestinal tract. Journal of Biological Chemistry, 66, ELIAS, E., GIBsoN, G. J., GREENWOOD, L. F., HUNT, J. N. and TRIPP, J. H. (1968). The slowing of gastric emptying by monosaccharides and disaccharides in test meals. Journal of Physiology, 194, FENTON, P. F. (1945). Response of the gastrointestinal tract to ingested glucose solution. American Journal of Physiology, 144, FREEMAN, C. P., NoARxEs, D. E., ANNIsoN, A. F. and HILL, K. J. (1968). Quantitative aspects of intestinal fat absorption in young pigs. British Journal of Nutrition, 22, GRAY, J. S., BRADLEY, W. B. and Ivy, A. C. (1937). On the preparation and biological assay of enterogastrone. American Journal of Physiology, 118, HUNT, J. N. (1956). Some properties of an alimentary osmoreceptor mechanism. Journal of Physiology, 132, HUNT, J. N. (1963) The duodenal regulation of gastric emptying. Gastroenterology, 45, HUNT, J. N. and KNOX, M. T. (1964). The action of potassium oleate and potassium citrate in slowing gastric emptying. Journal of Physiology, 171, HUNT, J. N. and KNox, M.T. (1968). Regulation of gastric emptying. Handbook of Physiology, sec. 6, vol. 4, HUNT, J. N. and MACDONALD, J. (1954). The influence of volume on gastric emptying Journal of Physiology, 126, HUNT, J. N. and PATHAx, J. D. (1960). The osmotic effects of some simple molecules and ions on gastric emptying. Journal of Physiology, 154, 254. HYD1EN, S. (1955). A turbidometric method for the determination of higher polyethylene glycols in biological materials. Kungliga Lantbruklshgskolans Annaler, 22, KosAxA, T., LIM, R. K. S., LING, S. M. and LrU, A. C. (1932). On the mechanism of inhibition of gastric secretion by fat. A gastric-inhibiting agent obtained from the intestinal mucosa. Chinese Journal of Physiology, 6, KvAsITsxn, A. V. (1951). Voprosy fiziologii pishchevareniya svinei, p Sel'khozgiz, Moscow. LIM, R. K. S. (1933). Observations on the mechanism of the inhibition of gastric function by fat. Quarterly Journal of Experimental Physiology, 23, MARBAIX, 0. (1898). Le passage pylorique. la Cellule, 14, MARKOWITZ, J., ARCHIBALD, J. and DowNIE, H. G. (1964). Experimental Surgery, 5th Edn., p Williams & Wilkins Co. QuiGLEY, J. P. (1941). A modern explanation of the gastric emptying mechanism. American Journal of Digestive Diseases, 10, QUIGLEY, J. P. and PHELPs, K. R. (1934). The mechanism of gastric motor inhibition from ingested carbohydrates. American Journal of Physiology, 109, THOMAS, J. E. (1957). Mechanics and regulation of gastric emptying. Physiological Reviews, 37, THOMS, J. S., CRIDER, J. 0. and MoGAN, C. J. (1934). A study of reflexes involving the pyloric sphincter and antrum, and their role in gastric evacuation. American Journal of Physiology, 109,

7 36 Reed and Kidder WERLE, J. M., BRODY, D. A., LIGON, E. W., READ, M. R. and QUIGLEY, J. P. (1941). The mechanics of gastric evacuation. American Journal of Phy8iology, 131, WILSON, T. H. (1962). Inte8tinal Ab8orption, p. 78. Philadelphia: W. B. Saunders Co. WILSON, T. H. and LANDAU, B. R. (1960). Specificity of sugar transport by the intestine of the hamster. American Journal of Phy8iology, 198,