Michela Edelbroek

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects

SummaryThe relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at — 2, 2, 5, 10, 15, 30, 45, 60, 75, 90, 105, 120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3±0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r=−0.55, p<0.05) and directly related to the retention in the distal stomach at 120 min (r=0.72, p<0.01). Peak plasma glucose was related to the amount emptied at 5 min (r=0.58, p<0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r=0.58, p<0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r=−0.56, p<0.05) and plasma insulin at 30 min (r=−0.53, p<0.05). Plasma insulin at 120 min was inversely related (r=−0.65, p<0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r=0.53, p<0.05). These results indicate in normal subjects that (i) gastric emptying accounts for about 34 % of the variance in peak plasma glucose after a 75-g oral glucose load (ii) plasma glucose levels at 120 min are inversely, rather than directly, related to gastric emptying (iii) the distal stomach influences gastric emptying of glucose.

The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite

BACKGROUND It is uncertain whether gastric emptying of fat is determined mainly by its physical characteristics or chemical composition. In particular, the intragastric distribution of extracellular fat and the importance of that distribution to gastric emptying of fat is controversial. The effects of posture on gastric emptying, intragastric distribution, and appetite after ingestion of a meal containing oil and aqueous phases was evaluated. METHODS Eleven volunteers consumed 60 mL 99mTc-(V)-thiocyanate-labeled olive oil and 290 mL 113mIn-labeled soup while sitting and while lying in the left lateral decubitus position. Hunger before and after the meal was recorded. RESULTS In the sitting position, oil emptied from the stomach more slowly (P < 0.01) whereas in the decubitus position oil emptied faster (P < 0.01) than the aqueous phase. Oil was preferentially retained in the proximal stomach when sitting (P < 0.01), and more oil was retained in the distal stomach in the decubitus position (P < 0.05). The amount of oil that emptied in the first 180 minutes was not different between the two postures. The aqueous phase emptied much more slowly (P < 0.01) in the decubitus position. At 120 minutes and 180 minutes, subjects were less hungry (P < 0.05) in the decubitus position. In the decubitus position, hunger at 120 minutes and 180 minutes was related to the retention of oil (r > or = 0.79; P < 0.01) in the stomach. CONCLUSIONS These results indicate that (1) gravity has a major effect on the intragastric distribution and relatively little effect on total stomach emptying of oil, and (2) postprandial hunger is affected by posture and, in the decubitus position, is inversely related to the amount of oil that has entered the small intestine.

Effects of duodenal distention on fasting and postprandial antropyloroduodenal motility in humans

BACKGROUND/AIMS Mechanoreceptors in the proximal small intestine may play an important role in the regulation of gastric emptying. Balloon distention of the duodenum causes fundic relaxation. The purpose of the present study was to determine the effect of stimulation of duodenal mechanoreceptors on both fasting and postprandial antropyloroduodenal motility in humans. METHODS Antropyloroduodenal pressures were recorded in 12 healthy volunteers with a sleeve-sidehole assembly, incorporating two balloons 5 and 20 cm distal to the pylorus. Duplicate proximal and distal duodenal balloon distensions with 10, 20, and 30 mL of air for 2.5 minutes were performed separately and in randomized order both during fasting and after a meal. RESULTS During fasting, proximal and distal distention at all volumes increased the number of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05), and the response to proximal distention was greater (P < 0.05). Postprandially, proximal and distal distention increased basal pyloric pressure (P < 0.05) with a greater response to proximal distention (P < 0.05), but had no effect on isolated pyloric pressure waves. Both during fasting and postprandially, there were more synchronous and less antegrade antral waves during distention (P < 0.05). The number of duodenal pressure waves increased during proximal (P < 0.05) but not distal distention. CONCLUSIONS Stimulation of duodenal mechanoreceptors by balloon distention has significant and region-dependent effects on antropyloroduodenal motility that vary between fasting and postprandial states.

Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects

Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0-20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose.

Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal region during intraduodenal lipid and antral tachygastria in conscious dog

The myoelectrical and motor response of the antropyloroduodenal region to intraduodenal nutrient stimulation or antral tachygastria represent useful models for, respectively, physiological and pathophysiological gastric stasis to test the efficacy of prokinetic drugs. We evaluated the effects of an intravenous bolus of cisapride (0.63 mg/kg) on the myoelectrical and motor response of the antropyloroduodenal region to an intraduodenal triglyceride emulsion (10% Intralipid, 0.5 ml/min) or antral tachygastria in conscious dogs. Intraduodenal lipid suppressed antral motility (P<0.05, compared to intraduodenal saline) and stimulated phasic pyloric contractions (P<0.01, compared to intraduodenal saline), a motor pattern known to be associated with delayed gastric emptying. During intraduodenal lipid stimulation cisapride virtually abolished all isolated pyloric motor events (P < 0.05) and stimulated antral and duodenal motility (P<0.05 for both) and antropyloroduodenal coordination (65% versus 15%;P<0.05). Antral tachygastria was associated with a higher number of isolated pyloric motor events in the fasted state [0.8 (0.7–1.1) per minute versus 0.2 (0–0.3) per minute;P<0.05], but not during intraduodenal lipid stimulation [1.1 (0.9–1.7) per minute versus 1.2 (1.0–1.9) per minute; NS]. Cisapride decreased the number and duration of spontaneous episodes of antral tachygastria during intraduodenal saline and lipid infusion (P<0.05 for both) and abolished the tachygastria-associated motor patterns. Cisapride induced a 20% decrease in the antral slow-wave frequency during intraduodenal saline and lipid, irrespective of gastric pacemaker rhythm. We conclude that: (1) cisapride overcomes feedback from small intestinal lipid receptors on myoelectrical and motor activities of the antropyloroduodenal region and decreases antral slow-wave frequency, and (2) cisapride inhibits antral tachygastria and tachygastria-associated motor patterns. These effects may contribute to the effective gastrokinetic properties of cisapride in physiological and certain forms of pathophysiological gastric stasis.

Stereospecific Effects of Intraduodenal Tryptophan on Pyloric and Duodenal Motility in Humans

BACKGROUND L-Tryptophan delays gastric emptying in animals to a greater extent than D-tryptophan, but none of the possible motor mechanisms responsible for this stereospecific effect have been evaluated. METHODS In 11 healthy volunteers antropyloroduodenal pressures were recorded in the fasted state with a sleeve/sidehole manometric assembly during 20-min intraduodenal infusions (2 ml.min-1) of isotonic L- and D-tryptophan (50 mM, pH 5.7) and normal saline (pH 5.5), given in randomized order. RESULTS Intraduodenal L-tryptophan increased basal pyloric pressure (p < 0.05), whereas D-tryptophan had no effect. In contrast, L- and D-tryptophan both stimulated (p < 0.05) localized phasic pyloric pressure waves, and there was no significant difference in the responses. The number of duodenal pressure waves was greater during infusion of L-tryptophan than during D-tryptophan (p < 0.05). CONCLUSION We conclude that intraduodenal tryptophan has stereospecific effects on pyloric and duodenal motility. Although the precise contribution of these differential effects to gastric emptying remains to be clarified, they may be partially responsible for the differences in gastric emptying of D-tryptophan and L-tryptophan.

Stereospecific effects of tryptophan on gastric emptying and hunger in humans

The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L‐enantiomer. The effects of D‐ and L‐tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L‐tryp (50 mmol/L), D‐tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at ‐2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L‐tryp and D‐tryp (P <0.05) and D‐tryp emptied faster than L‐tryp (P <0.005). Emptying from the proximal stomach was fastest for saline (P <0.05) and faster for D‐tryp than L‐tryp (P <0.005). Emptying from the distal stomach was faster for saline than both D‐ and L‐tryp (P <0.05). A reduction in hunger (P <0.05) and a non‐significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L‐tryp than after ingestion of D‐tryp (P <0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine.

Pyloric motility. Sleeve sensor versus strain gauge transducer.

Intraduodenal infusion of nutrients has been shown by intraluminal sleeve-sidehole manometry to suppress antral contractions and stimulate isolated pyloric pressure waves (IPPWs) in humans. It is still unresolved, whether these pyloric contractions occur within an otherwise quiescent zone of motor and electrical activity and whether the presence of the sleeve sensor itself affects this nutrient-associated response. In four conscious dogs, comparisons were made between paired recordings of myoelectrical and motor activities of the antropyloroduodenal region with serosal strain gauge transducers and extracellular bipolar electrodes in the presence and absence of an intraluminal manometric sleeve-sidehole assembly during intraduodenal infusions of saline and a triglyceride emulsion (Intralipid 10%, 0.5 kcal/min). Of 287 isolated pyloric pressure waves, detected by the manometric sleeve sensor, 75% were detected as isolated pyloric contractions by the strain gauge transducers and 72% occurred in the absence of electrical spike activity in the distal antrum or proximal duodenum. The lower incidence of isolated pyloric contractions (strain gauges) was related to: (1) insensitivity of the pyloric strain gauge transducer in comparison to the manometric sleeve sensor (10%), and (2) inability of the manometric sleeve-sidehole assembly to detect pressure waves in the distal antrum (7%) or proximal duodenum (8%) during antral or duodenal wall motion. The presence of the sleeve sensor itself did not affect the number of lipid-induced isolated pyloric contractions but increased their amplitude [median 9 (7–15) mN vs 4 (2–6) mN;P<0.05]. We conclude that: (1) most isolated pyloric pressure waves recorded by the manometric sleeve sensor represent contractions truly isolated to the pylorus, and (2) the presence of a sleeve sensor does not influence the number of isolated pyloric contractions.