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.     

Comparisons of the effects on satiety and eating behaviour of infusion of lipid into the different regions of the small intestine.

Food intake and feelings of hunger and fullness were monitored in paired studies carried out in two groups of six healthy non-obese male volunteers during infusion of isotonic solutions of either a 50% corn oil emulsion or saline into the jejunum or into the ileum. Infusion of the lipid emulsion at a rate of 1.2 ml/min (4.9 kcal/min) into either the ileum or the jejunum significantly reduced the period of eating (p less than 0.01) and the quantity of food consumed (p less than 0.01), but neither affected the rates of drinking or the amount of fluid consumed. Infusion of the lipid emulsion into the jejunum also significantly reduced the sensations of hunger before the meal (p less than 0.05), and the rate of ingestion (p less than 0.01). Ileal infusion did not influence these indices. The results suggest that jejunal and ileal infusion of lipid reduces the size of the meal that could be consumed possibly by inhibiting gastric emptying. The alleviation of hunger before ingestion and the slower rate of eating, however, suggests that jejunal lipid activates an additional mechanism that influences the appetite centre in the hypothalamus directly.     

Gastrointestinal adaptation to enhanced small intestinal lipid exposure.

Studies were performed on 20 male adult rats to investigate the effects of chronic intermittent infusion of lipid and physiological emulsifier into the distal small intestine on stomach to caecum transit time (SCTT) of the head of a test meal. SCTT was measured using environmental hydrogen analysis. Ileal lipid infusion normally delays gastric emptying and small intestinal transit (p < 0.001), but chronic intermittent infusion of lipid, given three times a week gradually reduced the delay in transit time until by four weeks it was no longer than control values. The lipid induced delay did not return during the four weeks after the chronic infusion had finished. Intermittent infusion of physiological emulsifier into the distal small intestine for four weeks did not change the control SCTT or the acute response to an ileal lipid infusion. SCTT of the head of the meal did not change in the four weeks after the physiological emulsifier infusion had stopped. In conclusion these results show that infusing rats intermittently with lipid for four weeks results in desensitisation of the mechanisms by which distal small intestinal lipid regulate SCTT of the head of a meal. This adaptation is not reversed within four weeks of withdrawal of the lipid infusion. These results emphasise the importance of assessing recent dietary history when assessing gastric emptying and small bowel transit times.     

The 'ileal brake' after ileal pouch-anal anastomosis

The aim of this study was to assess if infusion of oleic acid into the ileal pouch would slow gastric emptying and small-bowel transit, delay defecation, and increase plasma levels of enteroglucagon, neurotensin, or peptide YY in patients with colectomy and ileal pouch-anal anastomosis. Eight subjects with chronic ulcerative colitis who had undergone the operation were studied on 2 consecutive days. On 1 day, saline (154 mM NaCl) was infused into the ileal pouch, and on the other day emulsified oleic acid (152 mM) was infused. The subjects ate a 300-kcal mixed meal containing liquid labelled with 99mTc-DTPA. To assess small-bowel transit concurrently with gastric emptying, a second marker, 111In-DTPA, was instilled through a tube into the duodenum at the end of the meal. Transit of both markers was monitored scintigraphically. Infusion of oleic acid into the ileal pouch slowed gastric emptying and small-bowel transit, and delayed the time to defecation compared with saline infusion. Neither the ileal pouch infusion alone or the meal alone altered plasma levels of enteroglucagon, neurotensin, or peptide YY, but the combination of the oleic acid infusion and the meal increased the levels of all 3 hormones. It was concluded that an "ileal brake" on gastrointestinal transit is functional following ileal pouch-anal anastomosis. Oleic acid placed into the ileal pouch slowed gastrointestinal transit and delayed defecation, effects which may have clinical application. The mechanism mediating the ileal brake may in part be hormonal.     

How does dietary lipid lower blood alcohol concentrations?

To determine the mechanism, whereby food lowers blood alcohol concentrations, gastric emptying and blood alcohol profiles were measured in six healthy male volunteers after they had drunk a 200 ml solution of vodka and orange juice containing 0.5 g/kg alcohol. Subjects were studied on two separate occasions during infusion of isosmotic solutions of either Intralipid or saline into the ileum via an intestinal tube. Gastric emptying was significantly delayed by ileal infusion of fat emulsion and the peak blood alcohol concentration was significantly depressed. Similar effects were observed in three subjects when the solutions were infused into the duodenum. These results suggest that the reduction in alcohol absorption by food does not depend on the physical relationship between the alcohol and the food or between the food and the absorbing epithelium, but is probably caused by a delay in the delivery of alcohol to the small intestine, from where it is rapidly absorbed.     

Melatonin as a modulator of the ileal brake mechanism

OBJECTIVE: The gastrointestinal tract represents the most important extrapineal source of melatonin. Intestinal melatonin release is induced by the ileal passage of nutrients and could play a part in the control of postprandial gut motility. The specific aim of this study was to determine the putative role of melatonin in the "ileal brake" reflex, an important mechanism released by ileal lipids that regulates the gastric emptying of chyme. MATERIAL AND METHODS: Under general anaesthesia rats were fitted with ileal cannula exteriorized at the back of the neck. After a 1-week recovery, experiments were performed in conscious fasted animals. Rats were fed by gavage 1.5 ml casein hydrolyse plus 0.05% phenol red and either saline or Intralipid were continuously infused (2 ml/h) into the ileum. Gastric emptying was measured 50 min after ingestion by gastric lavage and determination of phenol red by spectrophotometry. The effects of melatonin (1 mg/kg) and melatonin antagonist S-22153 (dose-response study 0.2-25 mg/kg) were tested versus vehicle in paired experiments at 1-week intervals. RESULTS: Ileal infusion of lipids delayed gastric emptying. During ileal infusion of lipids, melatonin antagonist S-22153, but not melatonin, potentiated the delay in gastric emptying induced by the ileal brake mechanism. The inhibition of gastric emptying induced by S-22153 was dose related. Neither melatonin nor S-22153 had noticeable effects on gastric emptying during ileal infusion of saline. CONCLUSIONS: Our data suggest that melatonin, released in response to ileal lipids, exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying of nutrients.     

Ileal short-chain fatty acids inhibit transpyloric flow in pigs

BACKGROUND: Short-chain fatty acids (SCFA) found in the ileum after caecoileal reflux might trigger a physiologic ileal brake similar that induced by ileal nutrient infusion. This study evaluates gastric emptying and motility after ileal administration of SCFA. METHODS: In eight conscious pigs gastric emptying was evaluated by double dilution (liquids) and direct measurement of duodenal effluent (liquids and solids) during ileal infusions of SCFA and isotonic and hypertonic saline. Antropyloroduodenal manometry and flow were recorded concurrently. RESULTS: Ileal SCFA significantly delayed gastric emptying of liquids and solids. During SCFA infusion the emptying pattern of liquids was less pulsatile, and flow pulses had a smaller stroke volume than during isotonic saline. The antroduodenal pressure gradient was decreased, whereas pyloric tone was increased. A reduced number of antral pressure waves occurred together with an increased frequency of isolated pyloric pressure waves. CONCLUSIONS: Ileal SCFA infusion delays gastric emptying of liquid and solid as a consequence of a decreased antral and increased pyloric motility.     

Effect of bran, ispaghula, and inert plastic particles on gastric emptying and small bowel transit in humans: the role of physical factors.

BACKGROUND: Coarse bran is known to accelerate transit through the whole gut and to increase stool weight. This effect is much reduced by grinding the bran, suggesting that particle size influences gut motor patterns. AIMS: To compare the effect of 15 g coarse bran with 15 g inert plastic particles and 7 g of ispaghula on the gastric emptying and small bowel transit of a rice pudding test meal. SUBJECTS: 13 healthy volunteers. METHODS: Transit of 99mTc labelled rice studied by gamma-scintigraphy measuring gastric emptying and colonic arrival over 10 hours. Small bowel transit was estimated from the difference between time to 50% gastric emptying and 50% colonic arrival. RESULTS: Bran delayed gastric emptying by 22 (SEM 8) minutes compared with control values of 88 (SEM 6) minutes p < 0.05. Ispaghula and plastic particles had no significant effect. Small bowel transit was accelerated compared with control values of 322 (SEM 29) minutes, decreasing by 95 (29) minutes and 62 (22) minutes after bran and plastic particles respectively. Ispaghula again showed no significant effect. CONCLUSION: Coarse bran delays gastric emptying and accelerates small bowel transit. The marked acceleration of small bowel transit also seen with inert plastic particles may be due to increased upper gut secretions after stimulation of enteric nerves.     

Central nervous system effects of corticotropin-releasing factor on gastrointestinal transit in the rat

Corticotropin-releasing factor (CRF) administered into the lateral cerebral ventricle significantly inhibited gastric emptying and small bowel transit, but most markedly increased large bowel transit in a dose-related fashion in freely moving rats. Inhibition of gastric emptying induced by central administration of CRF was completely abolished by pretreatment of the animals with either the ganglionic blocking agent chlorisondamine or the opioid antagonist naloxone, or by noradrenergic blockade with bretylium, but not by truncal vagotomy. Either chlorisondamine, naloxone, or vagotomy--but not bretylium--reversed the inhibitory effect of central CRF on small bowel transit. Chlorisondamine or vagotomy, but neither bretylium nor naloxone, abolished the stimulatory effect of central CRF on large bowel transit. Neither hypophysectomy nor adrenalectomy altered the gastrointestinal motor responses induced by central administration of CRF. Intraperitoneal administration of CRF also significantly inhibited gastric emptying and stimulated large bowel transit but did not alter small bowel transit. These peripheral effects of CRF were not prevented by blockade of autonomic efferents with bretylium or chlorisondamine. It is concluded that (a) CRF acts within the central nervous system to delay gastric emptying, to inhibit small bowel transit, and to increase large bowel transit in freely moving rats and (b) CRF exerts these biological actions by modulation of the autonomic nervous system and, in part, by opioid pathways.     

Effect of bombesin on glucose-induced insulin release in humans

The effect of bombesin on basal and glucose-stimulated insulin release was studied in male healthy volunteers. Glucose was administered by oral, intravenous or intraduodenal route during saline or bombesin infusion (5 ng/kg/min for 60 min). The peptide had no significant effect on basal levels of glucose and insulin. However, during its administration, the insulin response and the expected rise in blood glucose after oral glucose load (50 g) were strongly inhibited, and the gastric emptying of liquids was significantly delayed. On the contrary, the insulin response to intravenous glucose (20 g) was significantly increased by bombesin without changes in plasma glucose levels. Finally, when glucose was infused into the duodenum, thus bypassing the stomach, the insulin response was significantly increased by the peptide. In this case, too, plasma glucose levels after glucose load were virtually identical during either bombesin or saline infusion. These data clearly demonstrate that the direct effect of bombesin on insulin release is stimulatory and suggest that the inhibitory effect observed after oral glucose is connected with the action of the peptide on gastric emptying, the delay of which slows the entry of glucose into the small bowel.     

Effect of Preinjury Large Bowel Emptying on the Inhibition of Upper Gastrointestinal Motility After Spinal Cord Injury in Rats

Spinal cord transection (SCT) inhibits gastrointestinal motility in rats. We evaluated the effect of preinjury large bowel emptying on this phenomenon. Male Wistar rats (N = 52) were fasted for 24 or 48 hr with water ad libitum and pretreated with lactose (0.8 g) or saline. Next, laminectomy followed or not by complete SCT between T4 and T5 vertebrae was performed. Phenol red recovery in the stomach and proximal, medial, and distal small intestine was determined 1 day later. In animals submitted to 24 hr fasting + saline, SCT increased gastric recovery by 42.8% decreased medial small intestine recovery by 56.2%, while 48 hr fasting + saline or 24 hr fasting + lactose prevented the inhibition of gastric emptying (GE) in SCT animals. The 48 hr fasting + lactose prevented the inhibition of both GE and gastrointestinal transit. SCT-induced inhibition of upper gastrointestinal motility may involve enhancement of inhibitory reflexes, which can be prevented by large bowel emptying.     

Ileal brake failure in streptozotocin-induced diabetic rat

BACKGROUND: Diabetes mellitus frequently alters gastrointestinal function, but the pathophysiology of the diabetic gut has not been fully elucidated. Our aim was to characterize the enterogastric modulation of gastric emptying in an experimental model of diabetic rat and to determine the putative consequences of impaired regulation on glycaemic control. METHODS: Studies were performed in streptozotozin-induced diabetic and control groups of male Sprague-Dawley rats. In rats fitted with chronic ileal cannulae, gastric emptying of a peptide meal was measured during ileal infusion of either lipids (ileal brake) or saline. The influence of the ileal brake mechanism on blood glucose levels after oral administration of a glucose solution was also evaluated. RESULTS: Diabetic rats exhibited a precipitous gastric emptying (80% +/- 3% versus 57% +/- 3% in controls; P < 0.05). Ileal lipids delayed gastric emptying in control (38 +/- 4%; P < 0.05 versus ileal saline) but not in diabetic animals (77 +/- 5%; N.S. versus ileal saline). As the ileal brake contributes to the management of postprandial blood glucose levels (114 +/- 4.9 mg/dL after ileal lipids versus 134 +/- 7.8 mg/dL after ileal saline in control rats; P < 0.05), the failure of this mechanism in diabetic rats worsens glycaemic control after feeding (455 +/- 20.4 mg/dL after ileal lipids versus 399 +/- 8.7 mg/dL after ileal saline; P < 0.05). CONCLUSION: Experimental diabetes impairs the ileal brake mechanism and disturbs gastric emptying. These abnormalities may contribute to difficult glycaemic control.     

Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit

BACKGROUND & AIMS: This study was designed to characterize [D-F(5)Phe(6)D-Ala(11)]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5-500 microg. kg(-1). h(-1)) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. METHODS: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. RESULTS: Intravenous BIM26226 potently inhibited gastric lag time (114 +/- 7 vs. 41 +/- 6 minutes [control]) and gastric emptying rate (0.11 +/- 0.02%/min vs. 0.26 +/- 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 +/- 41 vs. 262 +/- 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t(50%), 35 +/- 4 minutes), which BIM26226 inhibited significantly (t(50%), 64 +/- 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. CONCLUSIONS: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.     

Disturbed gastric and small bowel transit in severe idiopathic constipation

Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (¹¹¹In-containing pancake) and liquids (^99mTc-containing orange, juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal-up to 48% solid residue (median: 11% for patients and 0% for controls,P<0.01) and 40% of liquid (median 9% vs 0%P<0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal<4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min,P<0.01). Effectiveness of small bowel transit was assessed by the proportion of solids in the cecum at the time the stomach had emptied 50% of the solid meal; this was reduced in the patients (median: 6 vs 18%,P<0.01). All patients with normal gastric emptying had normal small bowel transit, and all those with delayed gastric emptying had prolonged small bowel transit. Colonic transit of the radioisotope was slow in all patients (head of the radioisotope column, cecum to stool, median: 96 vs 31 hr,P<0.01). Many patients with severe idiopathic constipation have a disturbance of gastric and small bowel transit that may be related to symptoms and that have implications for treatment.     

Simultaneous measurement of gastric emptying, small bowel residence and colonic filling of a solid meal by the use of the gamma camera

A method for determining the profiles of gastric emptying, small intestinal residence, and colonic filling of a solid test meal, labelled with 250 microCi 99mTechnetium sulphur colloid has been evaluated in nine healthy volunteers and six patients with a disturbance in bowel habit. Mean small bowel transit time was determined by deconvolving the rate of colonic filling with the rate of gastric emptying. In normal subjects, the stomach appeared to empty exponentially with a half time of 1.2 +/- 0.3 hours (mean +/- SD). Food reached the colon by 2.8 +/- 1.5 hours. The mean small bowel transit time was 4.0 +/- 1.4 hours. In most normal subjects, the colon appeared to fill in a linear fashion with approximately 16% food residues entering every hour, and the profile of colonic filling in normal subjects was similar to the profile of ileal emptying observed after feeding a similar radiolabelled solid meal to 14 patients equipped with terminal ileostomies. There was a highly significant correlation between the onset of breath hydrogen excretion and the appearance of radioactivity over the caecum (r = 0.88, p less than 0.01), though in one third of subjects the increase in caecal radioactivity preceded the rise in breath hydrogen concentration by more than 20 minutes. There was also a highly significant correlation between the mean transit time and values for colonic filling but not values for gastric emptying. Patients with irritable bowel syndrome who had diarrhoea tended towards short small bowel transit and early colonic filling, whereas patients who have constipation tended towards long small bowel transit and delayed colonic filling. This method offers a novel means of assessing small bowel transit time, small bowel residence and the profile of colonic filling in man.     

Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study.

background & aims: Opiate bowel dysfunction is a significant clinical problem. Our aim was to evaluate the ability of a peripheral mu-opioid antagonist, alvimopan, to reverse the effect of codeine on gastric, small-bowel, and colonic transit time in healthy volunteers. METHODS: Seventy-four healthy participants (43 women) were randomized in a double-blind, placebo-controlled manner to 1 of 4 groups: alvimopan 12 mg twice daily in the presence and absence of codeine sulfate 30 mg 4 times/day, or codeine or placebo alone. Gastric emptying, small-bowel, and colonic transit were measured by scintigraphy using a 99m-labeled technetium egg meal and 111-labeled indium charcoal delivered to the proximal colon via a delayed-release capsule. The primary end points for colonic transit were geometric center of the colonic counts at 24 hours and time for 50% ascending colon emptying. Analysis of covariance was used to assess the significance of the primary and secondary end points. RESULTS: Codeine delayed gastric, small-bowel, proximal, and overall colonic transit (P < .05). Alvimopan reversed codeine's effect on small bowel and colon (ascending colon and overall colonic transit). Alvimopan also accelerated overall colonic transit compared with placebo. Thus, the mean colonic geometric center at 24 hours was 2.33 with placebo/placebo, 3.25 with alvimopan/placebo (P < .05), 1.5 with placebo/codeine (P < .05), and 2.63 with alvimopan/codeine. Alvimopan did not reverse codeine's delay of gastric emptying. CONCLUSIONS: Alvimopan reverses codeine's inhibitory effect on small-bowel and colon transit and has potential for treatment of opiate bowel dysfunction. Alvimopan alone accelerates colonic transit, suggesting that mu-opiate mechanisms participate in the physiologic control of colonic transit.     

Adaptation of hydrogen analysis to measure stomach to caecum transit time in the rat

Excreted hydrogen analysis was used to measure stomach to caecum transit time of the head of a test meal in 120 rats fed by gavage. Results were compared with the distribution of a labelled test meal in the gastrointestinal tract of rats killed at different time intervals after gavage. Values for stomach to caecum transit were compatible with the distribution of labelled meals in 91% of animals, although in the remainder the hydrogen concentration had not risen even though food residues were in the caecum when the animals were killed. The technique gave reproducible results; the coefficients of variation for four studies carried out in each of six animals varied between 4 and 14%. A meal consisting of homogenised baked beans had a significantly shorter stomach to caecum transit time (88.1 +/- 4.5 min; mean +/- SE; n = 21; p less than 0.001) than an equivalent volume of Complan/lactulose (180.9 +/- 8.7 min; n = 13). This technique was used to investigate the effect of ileal infusion of a fat emulsion (20% Intralipid) via a chronically implanted intestinal cannula on the stomach to caecum transit time of a bean meal, in a series of paired studies carried out in six rats. Stomach to caecum transit time was significantly delayed during ileal infusion of 20% Intralipid compared with the control infusion of an isotonic saline solution (218.3 +/- 21 min v 106.7 +/- 33 min Intralipid v saline; n = 6; p less than 0.001).     

Ileal brake failure in streptozotocin‐induced diabetic rat

Background: Diabetes mellitus frequently alters gastrointestinal function, but the pathophysiology of the diabetic gut has not been fully elucidated. Our aim was to characterize the enterogastric modulation of gastric emptying in an experimental model of diabetic rat and to determine the putative consequences of impaired regulation on glycaemic control. Methods: Studies were performed in streptozotozin‐induced diabetic and control groups of male Sprague‐Dawley rats. In rats fitted with chronic ileal cannulae, gastric emptying of a peptide meal was measured during ileal infusion of either lipids (ileal brake) or saline. The influence of the ileal brake mechanism on blood glucose levels after oral administration of a glucose solution was also evaluated. Results: Diabetic rats exhibited a precipitous gastric emptying (80%?±?3% versus 57%?±?3% in controls; P?P?P?P?Conclusion: Experimental diabetes impairs the ileal brake mechanism and disturbs gastric emptying. These abnormalities may contribute to difficult glycaemic control.     

Reduced postprandial blood glucose levels in recently diagnosed non-insulin-dependent diabetics secondary to pharmacologically induced delayed gastric emptying

In a previous study we demonstrated that patients with recently diagnosed non-insulin-dependent diabetes mellitus (NIDDM) had significantly increased gastric emptying rates of glucose solutions compared with those of nondiabetic sex- and age-matched controls. This finding of rapid gastric emptying contrasts with the delayed gastric emptying often exhibited as a late manifestation of diabetes mellitus that is attributed to autonomic neuropathy. The purpose of this study was to determine, in seven of the patients previously studied, whether (1) an intravenous infusion of cholecystokinin-8 (CCK-8) would delay the gastric emptying of a liquid glucose meal and, if so, (2) whether the delay in gastric emptying would result in reduced postprandial blood glucose concentrations due to prolongation of the absorption of the glucose in the liquid meal. Each patient underwent two separate gastric emptying studies, one during a saline infusion and one during a CCK-8 infusion. Blood samples were obtained at 15-min intervals for measurement of glucose, insulin, CCK-8, and gastric inhibitory polypeptide (GIP) concentrations. The average gastric half-emptying time was 41 min with the saline infusion and 94 min with the CCK-8 infusion (P=0.0042). The average glucose concentration over the 2-hr period following glucose ingestion was 17.1 mmol/liter with the saline infusion and 14.0 mmol/liter with the CCK-8 infusion (P=0.0073). The average glucose excursion value over the 2-hr period was reduced from 5.6 mmol/liter to 3.7 mmol/liter with the CCK-8 infusion (P=0.0550). Average CCK-8 (P=0.0247) and GIP (P=0.0032) excursion values were significantly different when patients received the CCK-8 infusion compared to concentrations after the saline infusion. Agents that delay gastric emptying may have therapeutic applications in patients with NIDDM.     

Gastric emptying of solid food is most potently inhibited by carbohydrate in the canine distal ileum.

Although glucose sensors regulating the gastric emptying of liquid meals are uniformly distributed throughout the canine small intestine, some data suggest that the distal small bowel more potently inhibits gastric emptying of solid foods. The aims of this study were to compare (a) the inhibition of gastric emptying by glucose sensors in the proximal intestine with the feedback from the distal intestine, (b) these effects on the gastric emptying of solids vs. liquids, and (c) the inhibitory effect of unhydrolyzed starch with glucose. In 7 dogs with chronic duodenal fistulas, the second, third, and fourth quarters of small bowel were perfused via chronically implanted transmural catheters. Gastric emptying of either solids or liquids was tracked by gamma camera while gastric output was diverted out the duodenal fistula and the small bowel perfused with test solutions of glucose (0.06-2.0 mol/L), 0.15 mol/L NaCl, or 8.5% soluble starch. It was found that (a) gastric emptying of solids but not liquids was approximately 3 times more potently inhibited by glucose in the fourth quarter vs. the first or second quarter of small bowel, and (b) only hydrolyzed starch inhibited gastric emptying of solids.