Mobilisation of enterocyte fat stores by oral glucose in humans

BACKGROUND AND AIMS: When a high fat oral load is followed several hours later by further ingestion of nutrients, there is an early postprandial peak in plasma triacylglycerol (TG). The aim of this study was to investigate the location and release of lipid from within the gastrointestinal tract. METHODS: Ten healthy patients undergoing oesopho-gastro-duodenoscopy (OGD) were recruited. At t=0, all patients consumed a 50 g fat emulsion and at t=5 hours they consumed either water or a 38 g glucose solution. OGD was performed at t=6 hours and jejunal biopsy samples were evaluated for fat storage. A subgroup of five subjects then underwent a parallel metabolic study in which postprandial lipid and hormone measurements were taken during an identical two meal protocol. RESULTS: Following oral fat at t=0, samples from patients that had subsequently ingested glucose exhibited significantly less staining for lipid within the mucosa and submucosa of the jejunum than was evident in patients that had consumed only water (p=0.028). There was also less lipid storage within the cytoplasm of enterocytes (p=0.005) following oral glucose. During the metabolic study, oral glucose consumed five hours after oral fat resulted in a postprandial peak in plasma TG, chylomicron-TG, and apolipoprotein B48 concentration compared with oral water. CONCLUSION: After a fat load, fat is retained within the jejunal tissue and released into plasma following glucose ingestion, resulting in a peak in chylomicron-TG which has been implicated in the pathogenesis of atherosclerosis.     

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.     

Effect of ileal infusion of glycochenodeoxycholic acid on segmental transit, motility, and flow in the human jejunum and ileum.

The hypothesis that the presence of glycochenodeoxycholic acid (GCDC) in the human Ileal bile acid concentrations showed a 54.0 (9.3)% absorption of glycochenodeoxycholic acid by the been tested in healthy volunteers. Mean transit times, flow rates and intraluminal pressures in a 40 cm jejunal segment proximal (n = 6) and a 40 cm ileal segment distal (n = 6) to a GCDC infusion port were measured. During GCDC infusion (60 mumol/min) jejunal and ileal transit were markedly (p less than 0.05) delayed (31.6 (7.7), mean (SEM) v 14.5 (3.8) min and 37.0 (5.7) v 21.0 (3.5) min, respectively), segment volumes increased (141.1 (30.2) v 59.2 (9.9) ml and 173.2 (26.3) v 83.9 (9.5) ml; p less than 0.05), while flow rates did not change significantly (4.6 (0.6) v 4.5 (0.6) ml/min and 4.8 (0.5) v 4.2 (0.3) ml/min, respectively). Ileal pressures (distal to the GCDC infusion port) decreased (p less than 0.05) promptly (1.0 (0.1) min) after the start of GCDC infusion. Inhibition of jejunal motility was more gradual and reached significance (p less than 0.05) only 30 min after beginning of the infusion. Ileal bile acid concentrations showed a 54.0 (9.3)% absorption of glycochenodeoxycholic acid by the 40 cm ileal segment. These observations suggest the existence of an intestinal control mechanism in healthy man, whereby presence of glycochenodeoxycholic acid in the ileum inhibits motility and delays transit in the jejunum and ileum.     

Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers

The effect of ileal infusion of a lipid emulsion, containing 50% corn oil and 3% albumen, on food intake and satiety was measured in paired experiments carried out in 6 healthy volunteers. Subjects ate for shorter periods of time during ileal infusions of fat emulsion compared with control infusions of albumen and saline (25 +/- 1 vs. 32 +/- 3 min, mean +/- SEM) and consumed a smaller amount of food (670 +/- 23 g vs. 884 +/- 89 g) and energy (1016 +/- 79 kcal vs. 1591 +/- 228 kcal). The quantity of liquid drunk and the rates of eating and drinking were not significantly affected by the infusion of fat emulsion. In a further series of experiments carried out in 5 normal volunteers, ileal infusion of corn oil emulsions delayed gastric emptying compared with ileal infusion of albumen and saline (t1/2 = 203 +/- 48 vs. 68 +/- 12 min, p less than 0.02). The possibility that the observed reductions in food intake were related to the effect of absorbed fat was investigated in 6 healthy volunteers during intravenous infusion of either fat emulsion or isosmotic saline. Food intake was not affected by intravenous infusion of lipid. Our results suggest that lipid may interact with ileal receptors to induce early satiety and reduce the amount of food consumed. The earlier inhibition of food intake during lipid infusion is perhaps best explained by early gastric distention caused by delayed gastric emptying, though the data would not exclude the release of an ileal mechanism, which has a direct action on the satiety centers.     

Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans.

Cholecystokinin (CCK) has been proposed to serve as a satiety signal in animals and humans. To further explore the role of CCK in humans, the effect on satiety and eating behavior of a specific CCK-receptor antagonist, loxiglumide, that preferentially inhibits peripheral (CCK-A) receptors was investigated. In a randomized, blind, four-period latin square design, 10 subjects received intravenous saline (placebo) or loxiglumide (10 mg/kg per hour) with concomitant intrajejunal perfusions of isotonic saline or fat (containing 50% corn oil and 3% albumin). Food intake and plasma CCK concentrations were assessed, and subjects scored their feelings of hunger and fullness in paired experiments. In placebo-treated subjects, the duration of the meal was shorter during fat perfusion (30 +/- 2 minutes vs. 35 +/- 2 minutes; P less than 0.01; mean +/- SEM). The amount of food intake was reduced (361 +/- 31 g vs. 454 +/- 35 g; P less than 0.05), and fluid ingestion was inhibited (490 +/- 31 mL vs. 625 +/- 38 mL; P less than 0.01). Loxiglumide did not affect any parameter and did not change the pattern of responses. In loxiglumide-treated subjects there was a 4-5-fold elevation in plasma CCK levels. These results confirm that jejunal infusion of lipid reduces the size of the meal and stimulates early satiety. The data imply that these effects are not mediated through peripheral endogenous CCK under these conditions.     

Duodenal infusion of different nutrients and the site of gaseous stimulation influence intestinal gas dynamics

OBJECTIVE: Excessive intestinal gas can be involved in postprandial abdominal symptom generation, but whether the small bowel influences intestinal gas dynamics, depending on the ingested meal, remains to be demonstrated. We compare the intestinal response to a proximal and distal small intestinal gas challenge during different duodenal nutrient components. MATERIAL AND METHODS: We randomly studied 32 healthy subjects, twice, on different days with a gas mixture infused at 12 ml/min either directly into the proximal jejunum or into the ileum; during duodenal lipids, amino acids, glucose, at 1 kcal/min each, or saline (n=8 for each group). Gas evacuation was monitored continuously and abdominal perception and girth changes were assessed. RESULTS: In response to the jejunal gas challenge, duodenal lipids delayed intestinal gas clearance more potently than amino acids (733+/-26 ml and 541+/-108 ml final gas retention; p<0.001), but when gas was directly infused into the ileum the retained volumes were much smaller (271+/-78 ml and 96+/-51 ml; p<0.001). During duodenal glucose, intestinal gas clearance following jejunal or ileal gas infusion was not significantly influenced. Abdominal perception in response to the jejunal and ileal gas challenge only increased slightly during duodenal lipids (2.0+/-0.3 score and 2.3+/-0.6 score; p<0.05 versus control). CONCLUSION: Postprandial intestinal gas clearance is hampered by duodenal lipids and amino acids but not by glucose. Specific inhibitory effects are more pronounced when gas is infused into the jejunum, which underlines the importance of the small intestine in postprandial gas retention.     

Role of the Jejunum Versus Ileum on Intestinal Gas Dynamics During a Balanced Meal in Healthy Subjects

Under physiological conditions, the human gut adapts intestinal gas propulsion and evacuation to prevent intestinal gaseous complaints In this study we aimed to determine influences of the jejunum versus ileum on intestinal gas dynamics during a balanced meal. Paired studies were randomly performed with seven women and three men, ages 28–42. A mixed liquid meal was infused (1 kcal/min) into the duodenum. After 30 min, gas was infused (12 ml/min) into the jejunum or ileum for 150 min. Gas expulsion was measured, and perception and girth changes were assessed. Postprandial intestinal gas propulsion was uneventful and recovery complete, with −7± 58 and −92± 44 ml final intestinal gas retention for jejunal and ileal gas infusion, respectively. Neither significant differences in abdominal perception nor changes in abdominal girth were seen. During a balanced meal, intestinal gas is effectively propulsed aborally, and this does not depend on the site of the small intestinal stimulation.     

Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food

Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine.     

Effect of chronic ethanol ingestion on enterocyte turnover in rat small intestine.

Whether chronic ethanol ingestion significantly damages the small intestine remains controversial. To clarify this we have analysed the morphology of the small intestinal epithelium and quantified its renewal in chronically ethanol fed rats. Twenty adult male rats were pair fed for 28 days a nutritionally adequate liquid diet containing either ethanol as 36% of total calories or an isocaloric diet in which fat substituted for ethanol. Crypt cell production rate was determined in the jejunum and ileum by the metaphase arrest method. Weight gain and small intestinal morphology were similar in ethanol fed and control rats, but enterocyte turnover was significantly reduced in the jejunum (p less than 0.05) and ileum (p less than 0.01) of the ethanol fed rats. This effect of ethanol on the small intestine is probably systemic rather than local, because the changes in jejunum and ileum were similar, and it may contribute to the development of malnutrition in chronic alcoholics.     

The effect of jejunal meal feeding on gastroesophageal reflux

BACKGROUND: Postprandial gastric distention is frequently associated with transient lower esophageal sphincter relaxation and gastroesophageal reflux (GER). Since the role of nutrient perfusion into the jejunum in inducing GER is not well understood, we studied the effect of jejunal feeding on GER through a percutaneous gastrojejunal tube in patients with and without reflux esophagitis. METHODS: Nine stroke patients with reflux esophagitis were fed through a percutaneous gastrojejunal tube with either a liquid meal (2 kcal/2 ml/min) or saline for 2 h randomly on 2 separate days. An esophageal pH probe was placed 5 cm above the gastroesophageal junction to detect acid reflux. Six stroke patients without esophagitis were enrolled as controls. RESULTS: In both the patients with esophagitis and the controls, esophageal acid exposure (15.3% (4.9%-28.2%) versus 2.7% (0.0%-10.8%), P=0.003; 5.9% (0.5%-6.7%) versus 0.0% (0.0%-1.5%), P = 0.01) and events of acid reflux (5 (1-16) versus 2 (0-8), P = 0.02; 12 (3-17) versus 1 (0-4), P = 0.02) were significantly greater during jejunal meal feeding than during saline infusion. Furthermore, in the reflux patients, but not in the controls, acid clearance time was also greater during jejunal meal feeding than during saline infusion (2.9 min (0.5-9.6 min) versus 0.7 min (0.0-4.3 min), P = 0.04). CONCLUSIONS: We therefore conclude that jejunal nutrient infusion without gastric distention can induce GER in both patients with reflux esophagitis and controls. This implies that GER induced by jejununal nutrients may in part explain the incapability of jejunal tube feeding to prevent gastropulmonary aspiration in patients at risk.     

Effect of prefeeding lipid on food intake and satiety in man.

Experiments were carried out in normal volunteers to investigate whether preingestion of lipid reduces food intake. In the first set of experiments, 300 ml beef consomme soup with or without 60 g margarine was fed to each of six volunteers, followed 20 minutes later by either a low fat solid meal or a preselected appetising meal. Subjects were allowed to eat as much of the meal as they wished. Preingestion of the high fat soup had no significant effect on the consumption of either of the solid meals and did not influence sensations of hunger or fullness. As we have previously shown that prefeeding a fatty soup delays gastric emptying of a subsequent meal, this suggests that gastric distension may play a relatively minor role in regulating food intake. In the second set of experiments, we studied the effect of ingesting either a high fat breakfast (65 g fat, 927 kcal) or a similar low fat breakfast (8-1 g fat, 418 kcal) on the consumption of a preselected appetising lunch in six healthy volunteers. The high fat breakfast significantly reduced the amount of the meal eaten at lunchtime (p less than 0.02), the total energy intake from the meal (p less than 0.05) and the rate of eating (p less than 0.05) compared with the low fat breakfast. When the subjects were presented with their lunchtime meal they felt significantly less hungry after the high fat breakfast (p less than 0.05). Only a small proportion of either meal (15% of the high fat meal v 12% of the low fat meal) remained in the stomach and plasma glucose concentrations had returned to fasting levels. Plasma triglyceride concentrations were much higher at lunchtime after ingestion of the high fat breakfast (p<0.001). The energy intake from the breakfast and lunch combined was not significantly different on the high fat breakfast day, indicating that the energy consumption at lunch compensates for the amount eaten at breakfast. These results are compatible with the concept that the interaction of nutrients with small intestinal receptors may play a part in limiting food intake.     

Effects of cisapride on gastric emptying of oil and aqueous meal components, hunger, and fullness.

To evaluate the effects of cisapride on gastric emptying of extracellular fat and hunger and fullness 10 volunteers consumed a meal consisting of 60 ml technectium-99m (99mTc)-V-thiocyanate labelled olive oil and 290 ml indium-113m (113mIn) labelled soup after taking cisapride (10 mg four times daily orally) and placebo, each for four days, in randomised, double blind fashion. Gastric emptying was quantified scintigraphically. Hunger and fullness before and after the meal were evaluated using visual analogue scales. Cisapride accelerated gastric emptying of oil and aqueous components by reducing the lag phase mean (SEM) (20.3 (7.0) min v 40.7 (4.1) min (p < 0.05) for oil and 4.1 (2.5) min v 10.0 (3.1) min (p < 0.05) for aqueous). Cisapride had no effect on the post-lag emptying rate of oil. Treatment with cisapride was associated with reduced retention of oil in the proximal stomach (p < 0.05). Subjects were more hungry before ingestion of the meal while receiving cisapride (6.7 (0.9) v 3.9 (0.7), p < 0.001). The scores for hunger at 120 and 180 minutes were inversely related to gastric emptying of oil on both cisapride (r > -0.62, p < 0.05) and placebo (r > -0.86, p < 0.001). Fullness increased after the meal while receiving placebo (p < 0.01), but not cisapride and postprandial fullness was less with cisapride at (30 min; 0.4 (0.3) v 3.3 (1.0), p < 0.05). With placebo, but not cisapride, the score for fullness at 15 minutes was inversely related to emptying of the aqueous phase (r = 0.68, p < 0.05). These results show that in normal volunteers after ingestion of an oil/aqueous meal: (a) postprandial hunger is inversely related to gastric emptying of oil, while fullness is inversely related to gastric emptying of the aqueous phase, (b) cisapride affects the intragastric distribution and accelerates gastric emptying of both oil and aqueous meal components, and (c) cisapride increases preprandial hunger and reduces postprandial fullness.     

Effect of prostacyclin (PGI2) on water and solute transport in the human jejunum.

Prostacyclin is an arachidonic acid metabolite, synthesised throughout the gastrointestinal tract, which has different effects on water and electrolyte transport across a variety of mammalian gastrointestinal epithelia. Using a perfusion technique in the human jejunum of 11 healthy subjects in vivo, the effect of intravenous prostacyclin, 4 ng/kg/min, on jejunal water and solute transport from a glucose electrolyte solution was investigated. In the prostacyclin group (n = 5), prostacyclin was infused intravenously from 70-150 minutes, and buffer administered iv from 0-70 and 150-210 minutes. In the buffer group (n = 6), iv buffer was administered from 0-210 minutes. In the prostacyclin group, net jejunal absorption of water was inhibited from 90-120 min (p less than 0.05), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01), of sodium was inhibited from 90-120 min (p less than 0.05), 120-150 min (p less than 0.05), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01), and of chloride was inhibited from 90-120 min (p less than 0.05), 120-150 min (p less than 0.005), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01). Prostacyclin had no effect on net movement of glucose, potassium or bicarbonate. These results are consistent with a role for prostacyclin in the endogenous humoral regulation of water and electrolyte transport in the human jejunum.     

Sites of symptomatic gas retention during intestinal lipid perfusion in healthy subjects

BACKGROUND: Gas pooling within the gut may produce abdominal symptoms but the segment of the intestine responsible for gas retention is unknown. Our aim was to determine the role of the proximal and distal bowel in symptomatic gas accumulation using an experimental model of gas retention triggered by intraluminal lipids. SUBJECTS: Sixteen healthy subjects. METHODS: A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the intestine at12 ml/min for three hours and gas evacuation was continuously measured via an anal cannula connected to a barostat. Abdominal perception and girth changes were measured at 10 minute intervals. Lipids (1 kcal/min) were simultaneously perfused either into the duodenum (n = 8) or into the ileum (n = 8). Each subject was studied twice on separate days, with gas infused into the jejunum or ileum. RESULTS: Duodenal lipids produced retention of gas infused into the jejunum (646 (62) ml) but the volume retained was much smaller when gas was infused directly into the ileum (262 (90) ml; p<0.05). The effects on gas retention were even more pronounced during ileal perfusion of lipids (1546 (184) ml during jejunal gas infusion and 847 (142) ml during ileal gas infusion; p<0.05). Abdominal distension correlated with the volume of gas retained (r = 0.87; p<0.001). Healthy subjects tolerated gas retention, and significant symptoms (score 3.7 (0.8)) developed only during jejunal gas infusion plus ileal lipid perfusion when gas retention was very large. CONCLUSION: Intraluminal lipids induce intestinal gas retention, predominantly acting on the proximal small bowel.     

Gastric distension and duodenal lipid infusion modulate intestinal gas transit and tolerance in humans

OBJECTIVE: Patients with unexplained abdominal complaints often attribute their symptoms to intestinal gas and indicate that symptoms are exacerbated by ingestion of a meal. However, the mechanisms responsible are unknown. Our aim was to analyze the specific influence of two meal-related factors, gastric distension, and intestinal nutrients, on intestinal gas dynamics and tolerance. METHODS: In 35 healthy subjects, gas evacuation and perception of jejunal gas infusion (12 ml/min) were measured for 3 h, during simultaneous duodenal infusion of saline, as control, lipids at 1 Kcal/min, or gastric distension. RESULTS: Infusion of lipids into the duodenum induced gas retention (584 +/- 154 ml, p < 0.05 vs 161 +/- 86 ml after saline infusion) without perception (2.2 +/- 0.5 score), whereas gastric distension induced perception (score 5.6 +/- 0.4, p < 0.05 vs score 1.9 +/- 0.4 after saline) without gas retention (7 +/- 205 ml). CONCLUSIONS: Different meal-related factors exert specific effects on intestinal gas dynamics and tolerance, and these mechanisms may interact to produce postprandial gas symptoms.     

Role of cholecystokinin in the gastrocolonic response to a fat meal

The fat component of the meal is the major stimulant of the gastrocolonic response. The aim of this study was to characterize the mechanism of the gastrocolonic response after eating fat in healthy human volunteers. A bipolar clip electrode recorded spike activity (SP) from the distal colon. An immediate increase in colonic spike activity occurred after eating a fat meal (18.0 +/- 3.0 SP/30 min) (p less than 0.02). Spike activity remained elevated for 90 min after eating the fat meal (18.6 +/- 2.7 SP/30 min) (p less than 0.01). The intravenous infusion of naloxone or atropine inhibited the fat-induced increase in colonic motility. Cholecystokinin is a candidate mediator of the fat-stimulated gastrocolonic response. The intravenous infusion of the octapeptide of cholecystokinin (20 ng/kg . h) stimulated an increase in distal colonic spike activity (16.0 +/- 3.7 SP/30 min) (p less than 0.025). Intravenous atropine did not affect stimulation of colonic motility by the octapeptide of cholecystokinin. Continuous infusion of naloxone, however, did inhibit stimulation of colonic spike activity by the octapeptide of cholecystokinin. There was no cross-reactivity between opiate or muscarinic receptors. These data suggest (a) fat stimulation of the gastro-colonic response required a muscarinic and opiate receptor, and (b) octapeptide of cholecystokinin can stimulate colonic motility, but it is not the major mediator of the gastrocolonic response.     

Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion

OBJECTIVE: In healthy individuals, intraluminal lipids delay intestinal gas clearance, and this reflex is exaggerated in patients with irritable bowel syndrome (IBS). Our aim was to determine the site of action of abnormal lipid-induced reflexes in IBS. METHODS: In six patients with (IBS) predominantly complaining of bloating and in six healthy subjects, a mixture of gas (N2, O2, and CO2 in venous proportions to minimize diffusion) was infused (12 mL/min) either into the jejunum or into the ileum for 2 h, with simultaneous perfusion of lipids (0.5 kcal/min) into the proximal duodenum. Rectal gas evacuation was measured by a barostat. Abdominal perception (by a 0-6 scale) and girth changes were measured at 15-min intervals. The effects of jejunal versus ileal gas infusion were compared by paired tests in random order on separate days. RESULTS: IBS patients exhibited significant gas retention during infusion of gas into the jejunum (398 +/- 90 mL vs-210 +/- 105 mL in health, p < 0.05) but not during ileal infusion (-79 +/- 87 mL vs-79 +/- 78 mL in health, NS; p < 0.05 vs jejunal infusion). Gas retention during jejunal gas infusion in IBS patients was associated with significant abdominal distension (11 +/- 3 mm girth increment vs 0 +/- 1 mm during ileal gas infusion and 1 +/- 1 mm in health, p < 0.05 for both) and abdominal symptoms (3.6 +/- 0.6 score vs 2.6 +/- 0.7 score during ileal gas infusion and 1.6 +/- 0.5 score in health, p < 0.05 for both). CONCLUSIONS: In IBS patients intraluminal lipids impair intestinal gas clearance because of upregulated reflex inhibition of small bowel transit, without appreciable colonic effects.     

Regulation of gastric emptying by ileal nutrients in humans

Studies were carried out in 25 healthy male volunteers to investigate the effect of ileal infusion of solutions of different nutrient composition and osmolality on the profiles of a radiolabeled solid meal emptying from the stomach. Ileal infusion of a 50% corn oil emulsion or a 20% oleic acid emulsion slowed the rate of gastric emptying compared with ileal infusion of isotonic saline (0.9%). In contrast, infusion of either hypertonic saline (430 mosmol), distilled water, or isotonic solutions containing protein hydrolysate (8 g%) or glucose (50 mM) had no effect on the gastric emptying profile. These experiments support the hypothesis that the presence of unabsorbed lipid or fatty acids in the distal small intestine may delay gastric emptying, but suggest that sugars and proteins are ineffective. As infusion of both protein hydrolysates and lipid into the ileum can delay small bowel transit in humans, the data suggest that ileal regulation of gastric emptying and small bowel transit may be mediated by different mechanisms.     

Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion

The aim of this study was to define better the motor phenomena associated with the slowing of gastric emptying by a duodenal lipid infusion. Antral, pyloric and duodenal motility were recorded in 10 healthy subjects with a manometric assembly which incorporated multiple perfused side-holes and a sleeve sensor positioned astride the pylorus. The gastric emptying of a standard solid meal and the distribution of the ingesta between the proximal and distal stomach were monitored with a radionuclide technique. A triglyceride emulsion was infused into the duodenum for 45 min once 25% of the meal had emptied. The infusion caused significant slowing in the rate of gastric emptying (P less than 0.01). This slowing in gastric emptying was associated with the suppression of pressure waves in the distal antrum (P less than 0.01) and proximal duodenum (P less than 0.01), the induction of pressure waves isolated to a narrow pyloric segment (P less than 0.01), and a redistribution of ingesta from the distal to proximal stomach. These findings suggest that pressure waves isolated to the pylorus, changes in the intragastric distribution of ingested food, and changes in proximal duodenal motility may all act in concert with changes in antral motility to regulate the gastric emptying of solids.     

The antagonistic metabolite of GLP-1, GLP-1 (9-36)amide, does not influence gastric emptying and hunger sensations in man

OBJECTIVE: Glucagon-like peptide-1 (GLP-1 (7-36)amide) is an intestinal hormone that is released in response to meal ingestion. GLP-1 reduces postprandial gastric and exocrine pancreatic secretion and is believed to inhibit gastric emptying. Furthermore, GLP-1 may play a role in hunger and thirst regulation. In vivo, GLP-1 is rapidly (within minutes) converted into a metabolite, GLP-1 (9-36)amide, which has been shown to act as a GLP-1 receptor antagonist in vitro and in anaesthetized pigs. The purpose of this study was to assess the effect of infusion of GLP-1 (9-36)amide on hunger ratings and antral emptying of a meal. MATERIAL AND METHODS: Six healthy volunteers were tested in a double-blind, placebo-controlled fashion. Antral emptying of a liquid meal and hunger ratings were determined using ultrasound technology and visual analogue scale scoring during infusions of saline or GLP-1 (9-36)amide (5 pmol/kg body wt/min) resulting in supraphysiological concentrations. RESULTS: Infusion of GLP-1 (9-36)amide had no effect on gastric emptying or the sensation of hunger compared to saline. CONCLUSIONS: Our findings suggests that the rapid formation of the antagonistic metabolite does not influence gastric emptying and hunger ratings in humans even when it is present in supraphysiological concentrations.