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Am J Physiol Gastrointest Liver Physiol 292: G1099-G1104, 2007. First published January 4, 2007; doi:10.1152/ajpgi.00519.2006
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NEUROREGULATION AND MOTILITY

Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release

Reawika Chaikomin,1 Keng Liang Wu,1 Selena Doran,1 Karen L. Jones,1 Andre J. P. M. Smout,3 Willem Renooij,4 Richard H. Holloway,2 James H. Meyer,1 Michael Horowitz,1 and Christopher K. Rayner1,2

1Discipline of Medicine and 2Department of Gastroenterology, Royal Adelaide Hospital, Adelaide, Australia; and 3Department of Gastroenterology and 4Department of Surgery, University Hospital Utrecht, The Netherlands

Submitted 6 November 2006 ; accepted in final form 1 January 2007


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel technique that allows flow events to be quantified. Eight healthy volunteers were studied twice, in random order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60 min. Concurrently, glucose and 3-O-methylglucose (3-OMG) were infused into the proximal duodenum (3 kcal/min), with frequent blood sampling to measure glucose, 3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and propagated pressure wave sequences was reduced by hyoscine in the first 10 min (P < 0.01 for both), but not after that time. In contrast, there were markedly fewer duodenal flow events throughout 60 min with hyoscine (P < 0.005). Overall, blood glucose (P < 0.01) and plasma 3-OMG concentrations (P < 0.05) were lower during hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were initially (t = 20 min) lower during hyoscine (P < 0.05). In conclusion, intraluminal impedance measurement may be more sensitive than manometry in demonstrating alterations in duodenal motor function. A reduction in the frequency of duodenal flow events is associated with a decreased rate of glucose absorption and incretin release in healthy subjects.

small intestine; anticholinergic; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide

GLYCEMIC CONTROL IS A MAJOR determinant of the development and progression of microvascular, and probably macrovascular, complications of type 1 (10, 32) and type 2 (49) diabetes, and the importance of transient postprandial hyperglycemia to overall glycemic control is now recognized (13). Although it has been established that the rate of gastric emptying is a major determinant of the postprandial increase in blood glucose in healthy subjects (24) and patients with type 1 (30) and type 2 (26) diabetes, there is much less information about how much of the variation in the postprandial glycemic response is determined by flow patterns of chyme in the upper small intestine. Several studies in animal models (12, 17, 42) and in humans (8, 38, 46, 47) indicate that different patterns of motor activity in the small intestine influence the absorption of glucose from the lumen. We have reported a relationship between absorption of the glucose analog 3-O-methylglucose (3-OMG) and the number of duodenal waves, and particularly antegrade propagated wave sequences, in healthy humans (46) and patients with type 1 diabetes mellitus (38). Furthermore, pharmacological inhibition of small intestinal motor activity has the potential to affect glucose absorption (40).

Although manometric recordings from closely spaced sideholes within the gut provide detailed information about the organization of lumen-occluding contractions in space and time, they cannot measure contractions that are not lumen occlusive and at best allow incomplete inferences regarding the flow of luminal contents. Intraluminal impedance recording has the capacity to determine flow events by monitoring changes in electrical impedance between pairs of electrodes positioned within the gut lumen (33). The passage of a fluid bolus results in a fall in, whereas an air bolus increases, impedance; the transit of the bolus along a gut segment can be monitored by recordings from sequential electrode pairs. Intraluminal impedance recording is now well established and validated in the esophagus (33). The technique has also been applied in the duodenum (35) and has been used to characterize antropyloroduodenal flow events in healthy humans (43, 44) and abnormalities of duodenal chyme transport in patients with diabetic gastroparesis (34). Concurrent duodenal impedance and manometry recordings have recently been compared with the "gold standard" of videofluoroscopy for the detection of flow events in the human duodenum (25). The outcome of this study indicates that impedance has a greater sensitivity for detecting flow than manometry and, accordingly, is likely to represent the most suitable technique for prolonged evaluation of intestinal flow patterns, where videofluoroscopy would entail excessive radiation exposure.

The presence of glucose in the small intestine stimulates the release of several peptides, including insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) (45), which play a key role in determining the postprandial glycemic response. As with glucose absorption, there is little information as to how variations in flow patterns in the upper small intestine may influence their release.

We aimed to compare duodenal manometry and impedance recordings and to evaluate the impact on glucose absorption and incretin hormone release, when duodenal motor function was suppressed pharmacologically by the anticholinergic drug hyoscine butylbromide.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Subjects

Eight healthy men (age 27.9 ± 2.3 yr, body mass index 26.8 ± 0.7 kg/m2) were recruited by advertisement. No subject was taking medication known to affect gastrointestinal function. The protocol was approved by the Research Ethics Committee of the Royal Adelaide Hospital, and each subject provided written, informed consent.

Protocol

Each subject underwent paired studies, separated by an interval of 4–7 days, in single-blind, randomized order. Subjects attended the laboratory at 0900 following an overnight fast (14 h for solids and 12 h for liquids). At that time, a combined manometry and impedance assembly was introduced into the stomach through an anesthetized nostril and allowed to pass into the duodenum by peristalsis. The assembly incorporated a multilumen silicone manometry catheter (external diameter 4 mm) (Dentsleeve, Adelaide, Australia) with six duodenal sideholes spaced at 3-cm intervals and an additional sidehole for intraduodenal infusion located between the two most proximal manometric sideholes, in parallel with an impedance catheter with six electrode pairs spaced at 3-cm intervals (external diameter 2 mm) (Sandhill Scientific, Highlands Ranch, CO). The location of the manometric sideholes corresponded to the midpoint of each electrode pair (Fig. 1). The manometric sideholes were perfused with degassed water, and the position of the assembly was monitored continuously by measurement of the transmucosal potential difference (TMPD) from two additional saline-perfused sideholes, one in the duodenum (1.5 cm proximal to those used for pressure measurement) and the other in the antrum (3 cm more proximal again), using established criteria (i.e., antral TMPD < –20 mV, duodenal TMPD > –15 mV, difference > 15 mV) (20). This required the insertion of a 20-gauge saline-filled cannula subcutaneously in the forearm as a reference. When the catheter was positioned correctly, an intravenous cannula was inserted in each forearm, one for blood sampling and the other for infusion of hyoscine or saline.


Figure 1
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  		Fig. 1. Configuration of the manometry and impedance catheters used to evaluate duodenal pressures and flow events. TMPD, transmucosal potential difference. D1–D6, duodenal manometry sideholes; I1–I6, electrode pairs for impedance measurement.

 
Fasting duodenal motility was observed until 5 min after the onset of duodenal phase II. At this time (t = –5 min), 20 mg of hyoscine butylbromide (Buscopan, Boehringer Ingelheim Australia) made up to 10 ml in normal saline, or 10 ml of normal saline alone as a control, were infused intravenously over 2 min. At t = 0 min, an intravenous infusion of hyoscine butylbromide (20 mg made up to 60 ml with normal saline), or saline alone, was given over 60 min (i.e., 0.033 mg/min). This rate of hyoscine infusion was chosen to match the elimination rate of hyoscine in a 70-kg human (21). Concurrently (i.e., t = 0–60 min), an intraduodenal infusion of 45 g glucose together with 5 g 3-OMG, dissolved in water to a total volume of 200 ml, was given over 60 min ({equiv}3 kcal/min) via the duodenal infusion channel. At t = 60 min both the hyoscine butylbromide and intraduodenal glucose infusions ceased.

Venous blood was sampled every 5 min from t = –5 to t = 60, and then at t = 70, 80, 90, 105, 120, 150, and 180 min for measurement of blood glucose; every 10 min from t = 0 to t = 90 and then at t = 120 and 180 min for measurement of plasma 3-OMG; and at t = 0, 10, 20, 30, 40, and 60 min for measurement of plasma insulin, GIP, and GLP-1 concentrations. Heart rate was recorded every 10 min for the first 90 min then every 15 min until 120 min and every 30 min until 180 min.

Measurements

Both the manometric and impedance signals were recorded at a sampling rate of 30 Hz (Insight stationary system, Sandhill Scientific) and stored on a hard disk for subsequent analysis.

Manometric analysis. Manometric data were analyzed in an automated fashion, using previously described software (41). The frequency of duodenal waves ≥10 mmHg in amplitude (total number in all duodenal channels per 10 min) and propagated sequences of duodenal waves was analyzed, assuming a propagation velocity between 0.9 and 16 cm/s (38).

Impedance analysis. Impedance recordings were analyzed by two independent observers (R. Chaikomin and C. K. Rayner) who were blinded to the study conditions. A flow event was defined as a transient decrease in impedance of ≥12% from baseline (25) in at least three sequential electrode pairs (i.e., ≥6 cm) (35) (Fig. 2). Flow events were classified as either antegrade or retrograde (25, 35). The detection of flow events was compared between observers, and consensus was reached over discrepant observations.


Figure 2
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  		Fig. 2. Example of concurrent recording of intraluminal manometry (top 6 channels, D1–D6) and impedance monitoring (bottom 6 channels, I1–I6), demonstrating 3 flow events (a), of which 1 is associated with a propagated duodenal pressure wave sequence (b).

 
Blood glucose, 3-OMG, plasma insulin, GLP-1, and GIP concentrations. Blood samples for determination of plasma insulin, GLP-1, and GIP were collected in ice-chilled tubes containing EDTA and 400 kIU aprotinin (Trasylol; Bayer Australia, Pymple, Australia) per liter of blood. Plasma was separated by centrifugation and stored at –70°C for subsequent analysis. Blood glucose concentrations were determined immediately by using a portable glucose meter (Medisense Precision QID, Abbott Laboratories, Bedford, MA). 3-OMG concentrations were measured by gas-liquid chromatography (38). Plasma insulin concentrations were measured by ELISA immunoassay (Diagnostics Systems Laboratories, Webster, TX) (23) and plasma GLP-1 and GIP concentrations by RIA (36).

Statistical Analysis

Data were evaluated by repeated-measures ANOVA with treatment and time as factors, with post hoc comparisons in the event of significant treatment x time interactions. Student's paired t-test was used to compare baseline blood glucose and plasma peptide concentrations and areas under the curves for blood glucose and 3-OMG, calculated by the trapezoidal rule. A statistical software package (Statview 5, SAS Institute, Cary, NC) was used for all analyses. Statistical significance was accepted at P < 0.05, and data are presented as means ± SE.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
All subjects tolerated the study well, and the anticholinergic effect of hyoscine (increase in heart rate vs. saline infusion) was maintained at a stable level throughout 60 min of hyoscine infusion (mean heart rate during hyoscine 85 ± 5, and during saline 67 ± 4 beats per min, P < 0.005) and remained higher with hyoscine until t = 70 min. Subjects could not discriminate between the two study conditions, and none noticed a dry mouth or blurred vision during hyoscine infusion.

Duodenal Pressure Waves

There were fewer duodenal pressure waves with hyoscine compared with saline during the first 10 min (P < 0.005, treatment x time interaction). However, over 60 min, there was no overall difference (i.e., treatment effect) in the frequency of duodenal pressure waves (Fig. 3A). Similarly, there were fewer propagated pressure wave sequences with hyoscine compared with saline during the first 10 min (P < 0.01, treatment x time interaction), but again, over 60 min, there was no overall difference in the frequency of propagated pressure wave sequences (Fig. 3B). The mean amplitude of duodenal waves did not differ between study days, when compared over 60 min (27.7 ± 2.4 mmHg during hyoscine vs. 25.1 ± 1.7 mmHg during saline infusion) or at 10-min intervals (data not shown).


Figure 3
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  		Fig. 3. Effect of intravenous hyoscine on duodenal pressure waves (A), propagated pressure waves sequences (B), and duodenal flow events (C) during intraduodenal glucose infusion (solid bars, hyoscine; open bars, saline; *P < 0.05 for post hoc comparison of individual time points).

 
Duodenal Flow Events

The majority of duodenal flow events were antegrade (96 ± 2% for hyoscine, 94 ± 3% for saline). There were markedly fewer duodenal flow events with hyoscine compared with saline throughout 60 min (P < 0.005) (Fig. 3C).

Blood Glucose, and Plasma 3-OMG, Insulin, GIP, and GLP-1 Concentrations

There was no difference in baseline blood glucose or plasma insulin, GIP, and GLP-1 concentrations between the study days.

On both study days, blood glucose increased to a plateau at ~40 min, then declined as soon as the intraduodenal glucose infusion ceased (t = 60 min) and returned to baseline by ~90 min (Fig. 4A). Blood glucose concentrations were lower during hyoscine infusion compared with saline (t = 0–60 min) (P < 0.01). There was also a trend for the peak blood glucose concentration to be lower after hyoscine (9.6 ± 0.4 vs. 10.3 ± 0.5 mmol/l, P = 0.08).


Figure 4
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  		Fig. 4. Effect of intravenous (IV) hyoscine on blood glucose concentrations (A) and 3-OMG concentrations (B) during intraduodenal (ID) glucose infusion (bullet, hyoscine; {circ}, saline). *P < 0.05 for the period of IV drug administration (t = 0–60 min). {dagger}P < 0.05 for area under the 3-O-methylglucose (3-OMG) curve, t = 0–180 min.

 
3-OMG concentrations increased during intraduodenal glucose and 3-OMG infusion and continued to rise after the end of the intraduodenal infusion, with a later peak on the hyoscine day but similar, and declining, concentrations at 180 min (Fig. 4B). However, 3-OMG concentrations were lower during hyoscine infusion compared with saline (t = 0–60 min, P < 0.05), and the area under the 3-OMG curve over 180 min was also less on the hyoscine day (43 ± 4 vs. 51 ± 4 units, P < 0.05).

There was a progressive rise in plasma insulin during intraduodenal glucose infusion (t = 0–60 min), from 10 min during saline and from 20 min during hyoscine, so that plasma insulin was less with hyoscine compared with saline at t = 20 min (P < 0.05 treatment x time interaction) (Fig. 5A).


Figure 5
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  		Fig. 5. Effect of intravenous hyoscine on plasma insulin concentrations (A), plasma GLP-1 concentrations (B), and plasma GIP concentrations (C) during intraduodenal glucose infusion (bullet, hyoscine; {circ}, saline; *P < 0.05 for comparison of individual time points).

 
GLP-1 increased from 20 min during saline and from 30 min during hyoscine infusion (Fig. 5B). Although GLP-1 concentrations did not differ significantly over t = 0–60 min, GLP-1 was less at t = 20 min during hyoscine than saline (P < 0.05).

GIP concentrations increased from 10 min during saline infusion and from 20 min during hyoscine infusion, with lower concentrations during hyoscine compared with saline at t = 10 and t = 20 min (P < 0.0005, treatment x time interaction) (Fig. 5C).


   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Although the rate of gastric emptying has been established as a major determinant of postprandial glycemia (24, 26, 30), the impact of small intestinal motor function in this regard has hitherto received little attention and is poorly defined. In this study, intraduodenal pressure and impedance signals were recorded simultaneously while glucose was infused into the duodenum in healthy humans, in the presence and absence of the anticholinergic drug hyoscine butylbromide. The frequency of duodenal flow events (evaluated by impedance) was apparently suppressed by hyoscine much more markedly than that of duodenal pressure waves or propagated pressure wave sequences (evaluated by manometry). The disparity between impedance measurements and manometry in detecting alterations in flow during hyoscine infusion was marked and emphasizes the utility of small intestinal impedance monitoring to evaluate alterations in gastrointestinal transit in various disease states. Manometry detects phasic changes in pressure that result from lumen-occluding contractions, whereas impedance measurement allows inferences to be made regarding transit of boluses of electroconductive fluid between pairs of electrodes. Since luminal flow is affected by variations in intestinal tone and diameter (9), as well as by propagation of lumen-occluding contractions, it is not surprising there may be disparities between manometry and impedance recordings, as illustrated here in Fig. 3.

By infusing glucose directly into the duodenum, our study design allowed the specific evaluation of the effect of variations in small intestinal motor function on glucose absorption and incretin release, independent of the known effects of hyoscine on gastric emptying (48). Loperamide has been used to suppress small intestinal motor activity in a previous study of glucose absorption (40), but in rodent models this drug has the potential to inhibit the intestinal glucose transporter SGLT1 (27). Therefore we chose the anticholinergic drug hyoscine butylbromide, which is widely used to inhibit small intestinal motor activity in radiological and endoscopic procedures (4, 16), has a rapid onset of action (20–30 min), and has little central anticholinergic action. The rate of hyoscine infusion was selected to maintain a stable anticholinergic effect over 60 min (21), and the observed heart rate response suggests that this was indeed achieved. Use of the glucose analog 3-OMG, which is absorbed in the same way as glucose but not metabolized (18), allowed us to differentiate diminished glucose absorption from increased glucose utilization.

The suppression of flow events that what we observed was associated with attenuation of the rise in blood glucose and a diminished rate of small intestinal glucose absorption, as indicated by plasma 3-OMG (Fig. 4), as well as a delayed release of both the incretin hormones (GLP-1 and GIP) and insulin (Fig. 5). We believe that the slowing of intestinal transit by hyoscine diminished the rate of absorption of glucose, delayed the spreading of glucose over the full length of GIP-bearing mucosa in the duodenum and proximal jejunum, and postponed the arrival of glucose into the GLP-1-bearing mucosa in the more distal jejunum and ileum. Both the smaller area under the 3-OMG curve and the initial delay in insulin release during the hyoscine day are consistent with delayed absorption, rather than increased disposal of glucose, as the explanation for the difference in the blood glucose curves. Previous reports have demonstrated a strong relation between small intestinal motility and glucose absorption. Two studies in which glucose (39) or xylose (17) were infused into the small intestine reported increased absorption of carbohydrate when the infusion was given during periods of motor activity (phase II or III of the migrating motor complex) compared with motor quiescence (phase I). Manometric observations in humans have also supported a relationship between the absorption of 3-OMG and the frequency of small intestinal pressure waves and propagated pressure sequences (38, 46). Suppression of flow events by hyoscine could temporarily slow glucose absorption by initially restricting the area of the absorptive surface. Spreading of glucose by intestinal transit over longer lengths of gut would allow the recruitment of progressively more glucose transporters, so that the overall rate of glucose absorption into the systemic circulation is no longer restricted to a localized maximum of ~0.5 g per min over 30 cm of upper jejunum (14, 22, 31). In addition, the thickness of the unstirred water layer over the mucosal surface is affected by intraluminal flow rates, with luminal perfusion at higher rates resulting in a thinner unstirred water layer and thereby enhanced glucose absorption (28). It could be suggested that the suppression by hyoscine of pressure waves in the first 10 min might be at least as important as the reduction in flow events in its impact on glucose absorption. However, the 3-OMG concentration curves, which reflect the systemic appearance of glucose absorbed from the lumen, continued to diverge for up to 80 min, i.e., well after the period during which manometric events were suppressed, which argues in favor of the importance of flow events in determining glucose absorption. Although there appears to be some disparity between the profound inhibition of flow events by hyoscine and the more modest reduction in glucose absorption, it should be recognized that, even if long distance flow events were completely abolished, glucose absorption would continue within the limits of the small intestinal surface area exposed to glucose. Moreover, the impedance technique lacks the sensitivity required to identify flow events occurring over short distances, which have a role in facilitating glucose absorption.

Hyoscine attenuated the initial rises in GLP-1, GIP, and insulin. This could potentially be accounted for by inhibition of vagally mediated GLP-1 and GIP secretion, but the evidence for vagal control of incretin hormone release is limited (11). In rats, electrical vagal stimulation does not release GIP (6), whereas in dogs neither vagotomy (37) nor electrical vagal stimulation (19) affects GIP secretion in response to glucose. Rodent intestinal L cells, which secrete GLP-1, have muscarinic receptors, and atropine inhibits GLP-1 secretion in vivo in rats (3); atropine is said not to delay small intestinal transit in this species. GLP-1 secretion from a human L cell line in culture is also reportedly suppressed by muscarinic M1 and M2 receptor blockade (2), although, because these L cells were derived from a colonic adenocarcinoma line, the relevance of the observations to upper small intestinal L cells in vivo is unclear. The few reports regarding the effect of muscarinic blockade in humans indicate that atropine inhibits both GIP (1) and GLP-1 (1, 5) secretion after a meal, but this may reflect the delay in gastric emptying induced by atropine, rather than any direct inhibition of secretion, since incretin hormone release is critically dependent on the rate of entry of nutrients into the small intestine (7, 36). There is good evidence, on the other hand, that first-phase insulin secretion is under autonomic control (1) and therefore could be inhibited by hyoscine. An alternative, and more plausible, explanation for the delay of GLP-1 and GIP secretion in our study may be that the hyoscine slowed the flow of glucose into more distal segments of the small intestine. This may be particularly relevant for GLP-1, given that the density of L cells increases more distally in the gut (15), where GLP-1 is released by local contact of glucose (29). Delayed secretion of GLP-1 and GIP, as opposed to decreased glucose absorption per se, also seems likely to account for the plasma insulin profile during hyoscine infusion, which was also attenuated initially but did not differ from the saline day at 60 min, despite both blood glucose and plasma 3-OMG still being lower at this point. Conversely, suppression of vagally mediated GLP-1, GIP, and insulin secretion alone by hyoscine cannot explain the blood glucose profile, which would then be expected to be higher, rather than lower, than on the saline day, in the absence of any difference in glucose absorption. Studies are indicated to define more clearly the impact of intestinal flow on incretin action.

In summary, this study has established the utility of intraluminal impedance monitoring in detecting pharmacologically induced alterations in duodenal motor function and provides evidence that flow patterns of glucose within the small intestine impact on both the rate of glucose absorption as well as incretin hormone and insulin release. In view of our observations, the relevance of changes in impedance patterns to nutrient absorption in the small intestine in disease states should be explored in future studies. A particular priority is to determine the degree to which variations in small intestinal flow patterns influence postprandial glycemia in patients with diabetes.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported by awards from AstraZeneca and the Royal Australasian College of Physicians, the Sylvia and Charles Viertel Charitable Foundation, and the Faculty of Health Sciences, University of Adelaide, to Dr. Rayner, and by the National Health and Medical Research Council of Australia (NHMRC). Dr. Chaikomin's salary was provided by a scholarship from the Thai Government and the Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Dr. Jones's salary was funded jointly by Diabetes Australia and the NHMRC.


   FOOTNOTES
 

Address for reprint requests and other correspondence: C. Rayner, Discipline of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, SA, Australia 5000 (e-mail: chris.rayner{at}adelaide.edu.au)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Ahren B, Holst JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50: 1030–1038, 2001.[Abstract/Free Full Text]
  2. Anini Y, Brubaker PL. Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 144: 3244–3250, 2003.[Abstract/Free Full Text]
  3. Anini Y, Hansotia T, Brubaker PL. Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 143: 2420–2426, 2002.[Abstract/Free Full Text]
  4. Aschoff AJ, Gorich J, Sokiranski R, Rieber A, Brambs HJ, Kramer SC. Pancreas: does hyoscyamine butylbromide increase the diagnostic value of helical CT? Radiology 210: 861–864, 1999.[Abstract/Free Full Text]
  5. Balks HJ, Holst JJ, von zur Muhlen A, and Brabant G. Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab 82: 786–790, 1997.[Abstract/Free Full Text]
  6. Berthoud HR, Jeanrenaud B. Sham feeding-induced cephalic phase insulin release in the rat. Am J Physiol Endocrinol Metab 242: E280–E285, 1982.[Abstract/Free Full Text]
  7. Chaikomin R, Doran S, Jones KL, Feinle-Bisset C, O'Donovan D, Rayner CK, Horowitz M. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects. Am J Physiol Endocrinol Metab 289: E504–E507, 2005.[Abstract/Free Full Text]
  8. Cherbut C, Bruley des Varannes S, Schnee M, Rival M, Galmiche JP, and Delort-Laval J. Involvement of small intestinal motility in blood glucose response to dietary fibre in man. Br J Nutr 71: 675–685, 1994.[CrossRef][Web of Science][Medline]
  9. Cooper H, Levitan R, Fordtran JS, Ingelfinger FJ. A method for studying absorption of water and solute from the human small intestine. Gastroenterology 54, Suppl: 783–787, 1968.[Medline]
  10. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977–986, 1993.[Abstract/Free Full Text]
  11. Deacon CF. What do we know about the secretion and degradation of incretin hormones? Regul Pept 128: 117–124, 2005.[CrossRef][Web of Science][Medline]
  12. Defilippi C, Gomez E. Effect of casein and casein hydrolysate on small bowel motility and D-xylose absorption in dogs. Neurogastroenterol Motil 7: 229–234, 1995.[Web of Science][Medline]
  13. Del Prato S. In search of normoglycaemia in diabetes: controlling postprandial glucose. Int J Obes Relat Metab Disord 26, Suppl 3: S9–17, 2002.[CrossRef][Web of Science]
  14. Duchman SM, Ryan AJ, Schedl HP, Summers RW, Bleiler TL, Gisolfi CV. Upper limit for intestinal absorption of a dilute glucose solution in men at rest. Med Sci Sports Exerc 29: 482–488, 1997.
  15. Eissele R, Goke R, Willemer S, Harthus HP, Vermeer H, Arnold R, Goke B. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22: 283–291, 1992.[Web of Science][Medline]
  16. Elson EM, Campbell DM, Halligan S, Shaikh I, Davitt S, Bartram CI. The effect of timing of intravenous muscle relaxant on the quality of double-contrast barium enema. Clin Radiol 55: 395–397, 2000.[CrossRef][Web of Science][Medline]
  17. Fioramonti J, Bueno L, Ruckebusch M. Blood sugar oscillations and duodenal migrating myoelectric complexes. Am J Physiol Gastrointest Liver Physiol 242: G15–G20, 1982.[Abstract/Free Full Text]
  18. Fordtran JS, Clodi PH, Soergel KH, Ingelfinger FJ. Sugar absorption tests, with special reference to 3–0-methyl-D-glucose and D-xylose. Ann Intern Med 57: 883–891, 1962.[Abstract/Free Full Text]
  19. Greenberg GR, Pokol-Daniel S. Neural modulation of glucose-dependent insulinotropic peptide (GIP) and insulin secretion in conscious dogs. Pancreas 9: 531–535, 1994.[Web of Science][Medline]
  20. Heddle R, Fone D, Dent J, Horowitz M. Stimulation of pyloric motility by intraduodenal dextrose in normal subjects. Gut 29: 1349–1357, 1988.[Abstract/Free Full Text]
  21. Herxheimer A, Haefeli L. Human pharmacology of hyoscine butylbromide. Lancet ii: 418–421, 1966.
  22. Holdsworth CD, Dawson AM. The absorption of monosaccharides in man. Clin Sci 27: 371–379, 1964.[Web of Science][Medline]
  23. Horowitz M, Cunningham KM, Wishart JM, Jones KL, Read NW. The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects. Diabetologia 39: 481–486, 1996.[Web of Science][Medline]
  24. Horowitz M, Edelbroek MA, Wishart JM, Straathof JW. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia 36: 857–862, 1993.[CrossRef][Web of Science][Medline]
  25. Imam H, Sanmiguel C, Larive B, Bhat Y, Soffer E. Study of intestinal flow by combined videofluoroscopy, manometry, and multiple intraluminal impedance. Am J Physiol Gastrointest Liver Physiol 286: G263–G270, 2004.[Abstract/Free Full Text]
  26. Jones KL, Horowitz M, Carney BI, Wishart JM, Guha S, Green L. Gastric emptying in early noninsulin-dependent diabetes mellitus. J Nucl Med 37: 1643–1648, 1996.[Abstract/Free Full Text]
  27. Klaren PH, Giesberts AN, Chapman J, White SJ, Taylor CJ, Hardcastle PT, Hardcastle J. Effect of loperamide on Na+/D-glucose cotransporter activity in mouse small intestine. J Pharm Pharmacol 52: 679–686, 2000.[CrossRef][Web of Science][Medline]
  28. Lewis LD, Fordtran JS. Effect of perfusion rate on absorption, surface area, unstirred water layer thickness, permeability, and intraluminal pressure in the rat ileum in vivo. Gastroenterology 68: 1509–1516, 1975.[Web of Science][Medline]
  29. Little TJ, Doran S, Meyer JH, Smout AJ, O'Donovan DG, Wu KL, Jones KL, Wishart J, Rayner CK, Horowitz M, and Feinle-Bisset C. The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed. Am J Physiol Endocrinol Metab 291: E647–E655, 2006.[Abstract/Free Full Text]
  30. Merio R, Festa A, Bergmann H, Eder T, Eibl N, Stacher-Janotta G, Weber U, Budka C, Heckenberg A, Bauer P, Francesconi M, Schernthaner G, Stacher G. Slow gastric emptying in type I diabetes: relation to autonomic and peripheral neuropathy, blood glucose, and glycemic control. Diabetes Care 20: 419–423, 1997.[Abstract]
  31. Modigliani R, Bernier JJ. Absorption of glucose, sodium, and water by the human jejunum studied by intestinal perfusion with a proximal occluding balloon and at variable flow rates. Gut 12: 184–193, 1971.[Abstract/Free Full Text]
  32. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353: 2643–2653, 2005.[Abstract/Free Full Text]
  33. Nguyen HN, Silny J, Matern S. Multiple intraluminal electrical impedancometry for recording of upper gastrointestinal motility: current results and further implications. Am J Gastroenterol 94: 306–317, 1999.[CrossRef][Web of Science][Medline]
  34. Nguyen HN, Silny J, Wuller S, Marschall HU, Rau G, Matern S. Abnormal postprandial duodenal chyme transport in patients with long standing insulin dependent diabetes mellitus. Gut 41: 624–631, 1997.[Abstract/Free Full Text]
  35. Nguyen HN, Silny J, Wuller S, Marschall HU, Rau G, Matern S. Chyme transport patterns in human duodenum, determined by multiple intraluminal impedancometry. Am J Physiol Gastrointest Liver Physiol 268: G700–G708, 1995.[Abstract/Free Full Text]
  36. O'Donovan DG, Doran S, Feinle-Bisset C, Jones KL, Meyer JH, Wishart JM, Morris HA, Horowitz M. Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes. J Clin Endocrinol Metab 89: 3431–3435, 2004.[Abstract/Free Full Text]
  37. Ohneda A, Kobayashi T, Nihei J, Imamura M, Naito H, Tsuchiya T. Role of vagus nerve in secretion of gastric inhibitory polypeptide in dogs. Tohoku J Exp Med 147: 183–190, 1985.[Web of Science][Medline]
  38. Rayner CK, Schwartz MP, van Dam PS, Renooij W, de Smet M, Horowitz M, Smout AJ, Samsom M. Small intestinal glucose absorption and duodenal motility in type 1 diabetes mellitus. Am J Gastroenterol 97: 3123–3130, 2002.[CrossRef][Web of Science][Medline]
  39. Rayner DV. The relationships between glucose absorption and insulin secretion and the migrating myoelectric complex in the pig. Exp Physiol 76: 67–76, 1991.[Abstract]
  40. Samsom M, Benninga M, vanSteenderen L, Renooij W, de Smet M, Akkermans LMA, Smout AJPM. Inhibition of small intestinal motility decreases glucose absorption in humans (Abstract). Gastroenterology 116: G4659, 1999.
  41. Samsom M, Smout AJ, Hebbard G, Fraser R, Omari T, Horowitz M, Dent J. A novel portable perfused manometric system for recording of small intestinal motility. Neurogastroenterol Motil 10: 139–148, 1998.[CrossRef][Web of Science][Medline]
  42. Sarr MG, Kelly KA, Phillips SF. Canine jejunal absorption and transit during interdigestive and digestive motor states. Am J Physiol Gastrointest Liver Physiol 239: G167–G172, 1980.[Abstract/Free Full Text]
  43. Savoye G, Savoye-Collet C, Oors J, Smout AJ. Interdigestive transpyloric fluid transport assessed by intraluminal impedance recording. Am J Physiol Gastrointest Liver Physiol 284: G663–G669, 2003.[Abstract/Free Full Text]
  44. Savoye-Collet C, Savoye G, Smout A. Determinants of transpyloric fluid transport: a study using combined real-time ultrasound, manometry, and impedance recording. Am J Physiol Gastrointest Liver Physiol 285: G1147–G1152, 2003.[Abstract/Free Full Text]
  45. Schirra J, Katschinski M, Weidmann C, Schafer T, Wank U, Arnold R, Goke B. Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest 97: 92–103, 1996.[Web of Science][Medline]
  46. Schwartz MP, Samsom M, Renooij W, van Steenderen LW, Benninga MA, van Geenen EJ, van Herwaarden MA, de Smet MB, Smout AJ. Small bowel motility affects glucose absorption in a healthy man. Diabetes Care 25: 1857–1861, 2002.[Abstract/Free Full Text]
  47. Sjovall H, Hagman I, Abrahamsson H. Relationship between interdigestive duodenal motility and fluid transport in humans. Am J Physiol Gastrointest Liver Physiol 259: G348–G354, 1990.[Abstract/Free Full Text]
  48. Stacher G, Bergmann H, Havlik E, Schmierer G, Schneider C. Effects of oral cyclotropium bromide, hyoscine N-butylbromide and placebo on gastric emptying and antral motor activity in healthy man. Gut 25: 485–490, 1984.[Abstract/Free Full Text]
  49. The UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 352: 837–853, 1998.[CrossRef][Web of Science][Medline]




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