THE EFFECT OF ACUTE HYPERGLYCEMIA ON GASTRIC EMPTYING IN MAN

Transcription

1 GASTROENTEROLOGY 70: , 1976 Cpyright 1976 by The Williams & Wilkins C. Vl. 70, N.2 Printed in U.S.A. THE EFFECT OF ACUTE HYPERGLYCEMIA ON GASTRIC EMPTYING IN MAN 1. L. MACGREGOR, M.B., R. GUELLER, M.D., H. D. WATTS, M.D., AND J. H. MEYER, M.D. Department f Medicine, Veterans Administratin Hspital, and University f Califrnia, San Francisc, Califrnia Older wrk in man with meals f carbhydrates in water has indicated that such meals slw gastric emptying in prprtin t their smlarities. Nevertheless, different carbhydrates have been fund t have differing efficacies per millismle. One pssibility which wuld explain such discrepancies amng carbhydrates is that hyperglycemia induced by carbhydrate absrptin itself cntributes t the slwing f gastric emptying. T test this pssibility, nrmal subjects were made acutely hyperglycemic with intravenus lads f glucse during the ingestin f varius liquid test meals, and rates f gastric emptying f these meals were cmpared in the same subjects during perids f induced hyperglycemia with rates f gastric emptying under euglycemia cnditins. Induced hyperglycemia significantly slwed the rate f emptying f meals cntaining fat + prtein, r prtein, but did nt significantly alter emptying f meals cntaining nly N acl. It is cncluded that hyperglycemia des exert sme effect n gastric emptying, but that these effects f hyperglycemia are variably expressed, depending n the presence f ther factrs which themselves slw gastric emptying. Meals f glucse in water are emptied frm the human stmach expnentially, and rates f gastric emptying vary inversely with glucse cncentratin. 1 As with ther slutes, the effect f glucse cncentratin n gastric emptying has been attributed t regulatin by dudenal smceptrs.2 Nevertheless, varius slutes appear t affect these pstulated smceptrs differently. Fr example, even amng simple sugars, the degree f slwing f gastric emptying per millismle f sugar varies. 1 Mrever, starch, iscalric with glucse, slws gastric emptying t the same degree as glucse 3 even thugh such starch slutins are less smtically active, being incmpletely hydrlyzed in the upper small intestine where nly 5 t 10% is present as glucse and 60 t 90% as disaccharide. 4 Differences in effectiveness per millismle amng varius carbhydrates have been attributed t variable access f sugars r hydrlytic prducts f starch r sugars t the pstulated smceptr cells alng the prximal gut. 2 An alternative explanatin fr the differing efficacies f varius carbhydrates is that rates f gastric emptying are affected by hyperglycemia fllwing carbhy- Received March 11, Accepted July 30, Address requests fr reprints t: Ian L. MacGregr, M.B. (111H), Department f Medicine, Veterans Administratin Hspital, 4150 Clement Street, San Francisc, Califrnia This wrk was supprted by funds frm the Veterans Administrattin and Natinal Institutes f Health Grant 1 ROI AMI The authrs are grateful t Melvin Wng fr technical assistance. All subjects were studied with their infrmed cnsent under prtcls and A apprved by the Human ExperimentatIOn Cmmittee f the University f Califrnia, San Francisc. drate adsrptin. Thus, carbhydrates culd affect gastric emptying accrding t hw much they elevate pstcibal bld glucse cncentratins instead f r in additin t hw much they might affect lcal smceptrs in the gut. T test this hypthesis, we have studied nrmal subjects in whm we measured the effect f hyperglycemia n gastric emptying f several types f liquid test meals. Methds Measurement f Gastric Emptying Gastric emptying f a liquid test meal cntaining prtein and fat was measured using an intestinal marker technique with a duble lumen intestinal tube. The tube was psitined with the prximal prt just distal t the Ligament f Treitz and the distal prt 25 cm beynd. The test meal cntained plyethylene glycl (PEG). A secnd nnabsrbable marker, phenl red (PR), was infused cntinuusly thrugh the prximal prt f the intestinal tube at a cncentratin f 50 mg per 100 ml and a rate f 1.2 ml per min. Samples f 7 t 8 ml were cllected by siphnage thrughut each lo-min perid via the distal sampling prts. PEG and PR cncentratins in these samples were measured. The vlume rate f flw at the sampling site was calculated frm the measured cncentratin f PR in the jejunal samples as fllws: flw rate = Vi x Ci/Cj ml per min, where Vi = rate f PR infusin, Ci = PR cncentratin in the infused slutin, and Cj = PR cncentratin in jejunal aspirate. Frm the measured cncentratin f PEG in the jejunal aspirate and the vlume rate f flw, as calculated abve, the amunt f PEG passing the sampling site with time was calculated, and this measurement was taken as an index f gastric emptying. (A similar methd fr measurement f 190

2 February 1976 THE EFFECT OF ACUTE HYPERGL YCEMIA 191 gastric emptying rates f liquids has been described with perfusin and sampling sites in the dudenum." Hwever, preliminary studies suggested the dudenal perfusin site was nt satisfactry.) With ther liquid test meals f mre hmgenus nature (slutins f glucse, saline, mannitl, r milk-pwder digestssee belw), rates f gastric emptying were measured by the duble gastric sampling technique described by Gerge." PEG was added t the test meals; this secnd indicatr allwed calculatin f the rate f emptying f the meal (PEG) despite any pssible dilutin f the meal by gastric secretin and/r dudenal-gastric reflux. Thus, the Gerge technique was used t calculate intragastric vlume at time t (V t ) and 100 x V t x [peg It/PEG = percentage f meal remaining in the stmach at time t, where Vt = intragastric vlume (ml) at t, [peg It = intra gastric cncentratin (mg per ml) f PEG at time t; and PEG = amunt (mg) f PEG in the riginal meal. Test Meals The prtein-fat meal cnsisted f 63 g f nnfat dried milk pwder (Carnatin), 38 g f crn il (Mazla), and 2.5 g f PEG brught t 500 ml with distilled water. The smlality f the meal was 320 millismles per liter. A meal f milk pwder digest was prepared by disslving 63 g f nnfat dried milk pwder plus 2.5 g f PEG int 500 ml f 0.08 N HCI plus 40 mg per 100 ml f pepsin and incubating this mixture fr 4 hr at 37 C; digestin was then terminated by bringing the ph f the slutin t 7.0 with drpwise additin f 10 N NaOH. This meal apprximated the prtein cntent f the prtein-fat meal; prir peptic digestin was used t assure that n prtein wuld cagulate in the stmach and thus make the intragastric cntents nnhmgenus. The smlality f the neutralized digest was 475 mosm millismles per liter. Other meals cnsisted t 500 ml vlumes f 600 millismlar NaCl, mannitl, r glucse t which 2.5 g f PEG were added. All meals were taken rally except the meal f milk pwder digest which was instilled thrugh an rgastric tube. Design f Study T test the effects f hyperglycemia n gastric emptying, hyperglycemia was induced in nrmal fasting vlunteers with a blus intravenus injectin f glucse just befre the taking f a test meal; the blus injectin was fllwed by a cnstant intravenus glucse infusin which sustained the hyperglycemia thrughut mst f the test perid. Each subject served as his wn cntrl, taking the same test meal n anther day n which sterile 150 mm NaCl was substituted fr glucse during bth intravenus blus injectin and the subsequent intravenus infusins. Whenever pssible, tests were perfrmed with each subject n cnsecutive days, and the rder f intravenus glucse versus saline administratin was randmized amng subjects. Fr the final study, subjects were nt given intravenus glucse; instead, rates f gastric emptying f 600 millismlar ral glucse were cmpared with rates f emptying f 600 millismlar ral mannitl in each subject. Prtein-Fat Meal Six nrmal fasting subjects were intubated n the evening befre each f a minimum f fur studies. Every subject was given a lw and high lad f intravenus glucse. These lads cnsisted f an initial blus f 150 mg per kg fllwed by a cnstant intravenus infusin f 5 mg per kg per min (lw lad) r 10 mg per kg per min (high lad). The lw lad infusin was 10% glucse, the high lad infusin 20% glucse. Each glucse experiment was paired with a saline cntrl experiment (intravenus saline plus ral prtein-fat meal) perfrmed the day befre r after, in which the subjects received equal vlumes f intravenus 0.15 M NaCI in place f the glucse. One additinal subject was tested with the high glucse lad and a paired saline cntrl nly. Bth venus plasma samples and samples f jejunal cntent were cllected at regular intervals fr analysis fr 21/:1 hr fllwing the meal. Residual meal remaining in the stmach at 150 min was aspirated. The intestinal cntents were cllected int iced tubes; venus bld was cllected in heparinized tubes. Other Meals Other grups f 5 nrmal subjects received a lw intravenus glucse lad r intravenus saline when they ingested 600 millismlar NaCI r received a meal f milk pwder digest instilled int the stmach via rgastric tube. Sampling by the Gerge technique" was perfrmed every 10 min fr the first 60 pstcibal min, and every 15 min thereafter. Plasma glucse cncentratins were measured initially (fasting) and every 15 min thrughut the curse f the experiment. In the final study, each f 5 subjects was studied n tw ccasins, with 500 ml f rally ingested meals f 600 millismlar glucse and 600 millismlar mannitl, given in randm rder amng subjects n different days. As abve, gastric emptying n each ccasin was measured by the Gerge technique, and the time curse f plasma glucse cncentratins was als fllwed. Analytical Methds Plyethylene glycl. Plyethylene glycl (average Ml Wt 3,000 t 3,700 (Carbwax 4,000), Unin Carbide Crp., New Yrk) was determined by the mdificatin f the methd f Hyden 7 as described by Malawar and Pwell" except that half-vlumes were used, and a test tube shaker replaced the described five inversins fllwing the additin f the barium chlride-trichlracetic acid slutin. A shrt mix was reprducible and made n significant difference t the develped turbidity. The samples and standards were diluted with 0.25% nnfat dried milk pwder slutin instead f water. The prtein facilitated precipitatin after additin f the barium hydrxide and zinc sulphate, and allwed centrifugatin t replace filtratin. Phenl red. Phenl red was determined as described by McLed et al. 9 except that dilutins f standards and samples were made with 0.25% nnfat dried milk pwder slutin; and centrifugatin replaced filtratin as described under PEG assay. The Ba(OH)2-ZnSO. precipitatin step was mitted in the study using aqueus glucse, saline, and mannitl meals; the aspirate samples were centrifuged and diluted apprpriately in phsphate buffer. Glucse. Plasma glucse was estimated by the rth-tluidine methd as described by Dubwski. IO Osmlarity was measured using a Fiske smmmeter. Statistical Analysis Rate cnstants fr gastric emptying were calculated by determining the cefficients f the equatin y = A + Bx. Fr the prtein-fat meal: y = lgl (A - At) where A = ttal PEG recvery (%). At = percentage f PEG passed sampling site in time t. x = time in minutes at 10-min intervals fllwing lag time fr meal t reach sampling site. Fr gastric emptying using Gerge technique: y = lgl (100 - At); At = percentage f meal (PEG) having left percentage f the stmach in time t. x = time in minutes. The slpe (B) f this linear regressin is the rate cnstant fr gastric emptying (-K). Frm this value, the half-time f gastric emptying can be calculated Ty, = 0.301,O/K min.

3 192 MACGREGOR ET AL. Vl. 70, N.2 The regressin lines within each grup were statistically cmpared using analysis f variance." The crrelatin f the gastric emptying rates with bld glucse cncentratins was determined by linear regressin analysis between Tl> and mean plasma glucse, where y = Tl> in minutes, x = mean plasma glucse fllwing lag time fr meal t reach sampling site until the end f the study. The crrelatin cefficients derived fr these determinatins were tested fr significant differences frm zer by using mathematical tables." Results Site f intestinal infusin. Using 500-ml meals f 10% dextrse and cmparing the intestinal methd with the serial methd f Hunt,12 the intestinal methd f measuring gastric emptying was fund t be accurate nly when the tube was placed with the infusin prt beynd the dudenjejunal junctin (fig. 1). Mre prximal infusin resulted in reflux f the PR and dilutin in the meal-filled stmach with subsequent verrestimatin f the flw rates and meal (PEG) recvery. The effect f the dudenjejunal junctin as a barrier against reflux has been previusly demnstrated. 13 Effect f hyperglycemia n gastric emptying f the Prtein-Fat Meal. The reprducibility f the methd was tested by a cmparisn f the tw cntrl series, the semilgarithmic plts f the percentage f the PEG meal marker prximal t the jejunal sampling site, with time, being a mst superimpsable (fig. 2), and the derived rate cnstants being identical (table 1). The time curse f the plasma glucse cncentratins (fig. 3) shwed that with bth lads f intravenus glucse, the bld sugar cncentratins began t fall after 45 min and reached near fasting levels at 105 min with the lw glucse lad. The intersubject variability in handling the glucse is evident frm the large standard errrs. The intravenus glucse infusins slwed the rate at which PEG passed the sampling site (fig. 2). The mean lag phase f abut 40 min was the time required fr the meal t reach the sampling site. Using the semilgarithmic crrelatin f the percentage f PEG prximal t the sampling site, with time, i.e., crrespnding t the straight line plts fllwing the lag phase in fig. 2, the mean rate cnstants were calculated (table 1). The p values fr significance f difference frm cntrl are <0.005 fr the high glucse lad and <0.025 fr the lw glucse lad (analysis f variance). The mean half-times f gastric emptying calculated frm these data are 39.6 min fr bth grups f saline cntrls; 56.8 min fr the lw glucse lad; and 70.9 min fr the high glucse lad. The calculated linear regressin f the Tv, f gastric emptying in minutes, with mean plasma glucse cncentratins in mg per 100 ml, fr individual subjects, are given in table 2. Althugh nly fur pints f cmparisn were available fr mst subjects, the values f the linear crrelatin cefficients, r, indicate a gd crrelatin in the first 4 subjects (p <0.05). Effect f hyperglycemia n gastric emptying f ther meals. Frm the abve, it was evident that induced hyperglycemia slwed the gastric emptying f the meal cntaining fat and prtein. T determine whether this effect was perative with ther meals the experiment was repeated using the lw intravenus glucse lad with a 600-millismlar saline meal, and later a 600-millismlar meal f milk pwder digest. In each grup f subjects the lw intravenus glucse lad induced a similar time curse f hyperglycemia as in the abve experiments with the prtein-fat meal (data PERFUSION DISTAL TO LIGAMENT OF TREITZ PERFUSION PROXIMAL TO LIGAMENT OF TREITZ GASTRIC EMPTYING (%) - INTUBATION METHOD INTESTINAL FIG. 1. Effect f psitin f intestinal infusin site n accuracy f assessment f gastric emptying. Perfusin prximal t dudenjejunal junctin (pen circles) and distal t dudenjejunal junctin (clsed circles) cmpared t methd described by Hunt and Knx." Gastric emptying expressed as percentage f administered PEG recvered after varying time intervals fllwing meal ingestin. Infusin prximal t the Ligament f Tritz resulted in frequent verestimatin f the amunt f meal which had left the stmach (as cmpared with the Hunt methd) and such verestimatin was assciated with demnstrable reflux f the phenl red (PR) int the stmach, an event which did nt ccur when phenl red was infused beynd the Ligament f Treitz.

4 February 1976 THE EFFECT OF ACUTE HYPERGLYCEMIA 193 nt shwn, see fig. 3). Yet the hyperglycemia did nt significantly slw gastric emptying f hypertnic saline (table 1) as the regressin lines did nt significantly differ whether glucse r saline was given intravenusly. When the experiment was repeated using the milk pwder digest meal in place f saline there was a statistically significant (p <0.01, analysis f variance) reductin in the rate cnstant f gastric emptying when glucse was given intravenusly. Oral glucse versus ral mannitl. A direct cmparisn was made between rates f emptying f ral 600 millismlar glucse versus ral 600 millismlar mannitl in a further 5 subjects. The hypertnic glucse meal induced an average peak. n Cl 100 c E 60 n 40 E x () w c Q) u... Q) Lw Glucse I:r -ll. High Glucse... Sline Cntrl Lw Glucse 0-0 S line Cntrl High Glucse TIME (minutes' FIG. 2. Illustratin f semilgarithmic plt f percentage f plyethylene (PGE) prximal t sampling site versus time in experiments with prtein-fat meal. Plts are f mean values (high glucse lad, seven subjects; lw glucse lad, six subjects). Figure illustrate lag time f 40 min and linearity f semilgarithmic plt versus time after the lag phase. Such linearity was fund in all subjects with all meals, but in later experiments using the Gerge technique with ther meals (see text), a lag phase was nt nted. rise in bld glucse f 139 mg per 100 ml at 45 min (fig. 4). This was lwer than that prduced with the lw dse intravenus glucse infusin (fig. 3). Statistical cmparisn f the regressin lines fr gastric emptying shwed that the glucse meal empties significantly mre slwly (p < 0.05) than the mannitl meal (table 1). The derived Tv, values fr emptying were 29.2 min and 20.1 min fr the glucse and mannitl meals, respectively (table 1). Discussin The great advantage f the described methd f determing gastric emptying rates by the intestine perfusin technique is that the curse can be fllwed ver a perid f time, and gastric emptying can be crrelated with small intestinal events such as bile flw and pancreatic secretin. 5, 14 This differs frm the serial test meal f Hunt 12 in which the amunt f meal remaining in the stmach can be determined nly at ne arbitrary time, as gastric vlumes remaining are measured n remval f cntents frm the stmach. The methd described by Gerge 6 which measures the time curse f intragastric vlumes has similar advantages ver Hunt's methd, but we have been cncerned abut the accuracy f this technique with a meal f the cmpsitin we used in the intestinal intubatin study, which has an aqueus phase, an il phase, and a slid phase wing t cagulatin f milk prtein in the stmach, as the accuracy f the Gerge technique depends n cmplete mixing f the added indicatr with the gastric cntent. The milk pwder digest did nt cagulate in the stmach, and the duble sampling technique was satisfactry with this meal. PEG is an aqueus phase indicatr, and the rates f gastric emptying we have measured are f the aqueus phase f the fat-cntaining meal. Slwer emptying f the fat phase f a similar meal has been nted by thers15 using similar techniques. The mean recvery f PEG in the intestinal intubatin studies was 111 % with n significant difference between grups (fig. 2). This verestimatin is accunted fr by the binding f the PR t meal prtein: a small amunt f TABLE 1. Rate cnstants and half-times fr gastric emptying Experiment Subjects Rate cnstanta Pvalue' T a Prtein-fat meal + High glucse iv Lw glucse iv Saline iv High glucse cntrl Lw glucse cntrl millismlar NaCI meal + Lw glucse iv Saline iv Milk pwder digest + Lw glucse iv Saline iv millismlar meals f: Glucse 5 0.Ql03 Mannitl < < > < < a Units f rate cnstant are lg,. (percentage emptied) per min; T" is half-time in minutes. P value is difference frm apprpriate cntrl value (analysis f variance).

5 194 MACGREGOR ET AL. Vl. 70, N E 250 UJ V') 200 U => --' () TIME (minutes) FIG. 3. Time curse f plasma glucse cncentratins (milligrams per 100 m!) fllwing intravenus blus and during intravenus infusin f high glucse lad (pen circles) and lw glucse lad (triangles). The value fr saline (clsed circles) represents the cmbined cntrls fr the high glucse and lw glucse lads. Values represent mean ± SEM. TABLE 2. Linear regressin between calculated T.", (minutes) and mean plasma glucse (mg per 100 ml)" Subject Regressin p M.J. y X 0.99 < 0.01 J. M. y X 0.98 < J. N. y X 0.95 < M.' y X 0.91 < 0.01 C. D. y X 0.86 >0.05 H.W. y X 0.71 > 0.05 " Data frm experiments with prtein-fat meal (see text); r linear crrelatin cefficient; P level f statistical significance f crrelatin ; y = T.",; x = mean plasma glucse., All subjects had nly 4 pints f analyses except subject 1. M., wh had 7. bund PR precipitates with the prtein during measurement f the PR cncentratin, and thus gives an underestimate f phenl red cncentratin with an verestimate f jejunal flw rates. 16 The present study has unequivcally demnstrated that hyperglycemia induced by intravenus glucse infusins slws gastric emptying f the prtein-fat meal. Mrever, regressin analyses indicated that the degree f slwing f gastric emptying f the prtein-fat meal culd be crrelated with the mea!! plasma glucse cncentratins in fur f six subjects (table 2). Althugh n such crrelatin was fund in subjects C. D. and H. W., in C. D., bth the lw and the high lads f intravenus glucse nearly cmpletely inhibited gastric emptying during mst f the hyperglycemic perid; while in H. W., neither glucse lad prduced much hyperglycemia r slwing f gastric emptying. We had selected the prtein-fat meal because it cntained substances nrmally eaten alng with carbhydrate. Because hyperglycemia slwed the emptying f this meal f dietary fdstuffs, we speculate that such an effect may pertain t nrmal feeding cnditins as the bld glucse levels btained with the lw glucse lad are within the nrmal range seen after eating mixed meals cntaining carbhydrate. Bth ingested fat l7 and prtein ls are knwn t slw gastric emptying. Thus, the results with the prtein-fat meal culd have reflected sme interactin f hyperglycemia with ther mechanisms (fat, prtein) which slw gastric emptying. T check this pssibility, the effect f hyperglycemia n the gastric emptying f saline was measured in anther grup f 5 subjects. N statistically significant effects f hyperglycemia were demnstrated althugh there was a tendency fr the glucse t slw emptying (table 1). This negative result suggested that indeed the effects f hyperglycemia n emptying f the prtein-fat meal might have been peculiar t this particular test meal. Hwever, yet anther set f experiments cnfirmed that hyperglycemia slwed emptying f a prtein meal (milk pwder digest). In summary, induced hyperglycemia significantly and appreciably slwed gastric emptying f test meals cntaining prtein with r withut fat. Significant effects f hyperglycemia n the emptying f saline meals culd nt be detected in the number f tests perfrmed. It is nt knwn by what mechanisms hyperglycemia affected gastric emptying f prtein fat r prtein digest meals. Althugh hyperglycemia usually evkes the release f endgenus insulin and the suppressin f endgenus pancreatic glucagn,19 insulin is knwn t augment, rather than reduce, gastric mtility, but acts by virtue f its hypglycemia actin, 20 while glucagn reduces gastric mtility.21 Gastrin, which slws gaetric emptying f liquids,22 was suppressed by the hyperglycemia. 14 The knwn hrmnal effects f hyperglycemia are thus in the ppsite directin frm what was bserved. It is pssible therefre that hyperglycemia slwed gastric emptying thrugh neural mechanisms, but there is n cnclusive prf f such a pstulate. Whatever the mechanisms respnsible, the results suggest that hyperglycemia alne exerted nly weak effects n gastric emptying, but that these effects were greatly augmented Q) '" u ;;;) (5 E '" CL: "... 0 """"... 1'... 1 I'- I' " 80 Oral Mannitl y---,( r - - -, r Minutes FIG. 4. Time curse f plasma glucse after ral glucse and ral mannitl meals.

6 February 1976 THE EFFECT OF ACUTE HYPERGL YCEMIA 195 by ther inhibiting mechanisms; viz. dietary fat and/r prtein in the upper gastrintestinal tract. The demnstratin that hyperglycemia slws gastric emptying, an effect prbably related t the degree f elevatin f the bld sugar, is nt a radical departure frm existing data. In 1962, Aylett 23 cncluded that elevatin f the bld glucse slwed gastric emptying. Her methd invlved manipulatin f the bld glucse with glucagn, insulin, and ral r intravenus glucse, and emplyed a mdificatin f Hunt's methd 12 using a water meal. Hwever, the effect f intravenus glucse was measured n nly ne ccasin in each f fur subjects, and the small number f subjects, tgether with the large intersubject variability, left sme dubt as t the validity f her cnclusins. Because mst f the present findings, as well as thse f Aylett, indicated an effect f hyperglycemia n gastric emptying, it was cnsidered pssible that the hyperglycemia effect f rally ingested glucse may cntribute t regulatin f gastric emptying f glucse meals in additin t any regulatry prcesses within the gastrintestinal tract, such as smceptive prcesses. Fr this reasn, the rate f emptying f a 600-millismlar glucse meal was cmpared t that f a 600-millismlar mannitl meal in the same subjects. Mannitl was used as a cntrl as it is smtically active, but has n hyperglycemic effects. The 600-millismlar mannitl meal emptied significantly mre quickly than the paired glucse meal (table 1). Whether the slwer emptying f the glucse meal was related t the mdest hyperglycemia induced by the glucse (fig. 4) cannt be stated with certainty, but is supprted by the freging experiments. The 600 millismlar NaCl left the stmach at faster rates than either 600-millismlar glucse r 600 millismlar mannitl; the mean rate cnstant fr the saline meal (with simultaneus intravenus saline) was mre than twice that f glucse and 11/2 times that f mannitl (Table 1). Althugh such cmparisns are nt strictly valid, as subjects cmprising the grup tested with meals f mannitl and glucse differed frm thse tested with NaCl meals, the differences indicate that saline affected gastric emptying rates differently frm issmtic glucse r mannitl, a finding nted previusly by ther. 14 It is difficult t recncile these differences amng varius issmtic meals with any simple r unqualified thery f smceptive cntrl. T explain such discrepancies, Hunt 2 has prpsed that gut smceptr cells have differing permeabilities t glucse versus NaCl. It is knwn that bth glucse and NaCl are transprted acrss intestinal absrptive cells, whereas mannitl is relatively impermeable t the same cells. 15 If the gut smceptr cells share these same permeability characteristics with the bulk f the gut mucsal cells, then the present findings (that 600 millismlar glucse emptied mre slwly than 600 millismlar mannitl, but bth emptied much mre slwly than 600 millismlar NaCl) are nt cnsistent with these permeability characterisitics. Hwever, the prblem is nt easily reslved, because the permeability characterisitics f the pstulated smceptr cells cannt be directly examined. We believe that a vast amunt f evidence des supprt the general cncept that gastric emptying is regulated by sme srt f smceptive cntrl. 2 Hwever, we als believe there are enugh anmalies in the behavir f varius meal slutes t suggest that such regulatin is prbably multifactrial. Thus, the present experiments indicate that glucse may slw gastric emptying by virtue f the hyperglycemia it induces after absrptin. In additin ral glucse mst likely activates lcal regulatry prcesses frm within the gastrintestinal tract. While these lcal regulatry prcesses may be smceptive in nature, ther pssibilities must be cnsidered, such as the release f gut hrmnes.26, 27 The present experiments d nt define hw much the slwing f glucse meals is affected by lcal gut factrs versus hyperglycemia; they merely indicate that hyperglycemic effects may be bserved under certain circumstances, mst especially when ther meal cnstituents (fat plus prtein, r prtein) are als perating t slw gastric emptying. REFERENCES 1. Elias E, Gibsn GT, Greenwd LF, et al: The slwing f gastric emptying by mnsaccharides and disaccharides in test meals. J Physil 194: , Hunt IN, Knx MT: Regulatin f gastric emptying. In Handbk f Physilgy, sect. 6 Alimentary Canal, vl. 4. 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