Effects of gastric distension on blood pressure and superior mesenteric artery blood flow responses to intraduodenal glucose in healthy older subjects.

Postprandial hypotension occurs frequently and is associated with increased morbidity. Gastric distension may attenuate the postprandial fall in blood pressure (BP). Using a barostat, we sought to determine the effects of gastric distension on BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow responses to intraduodenal glucose in eight (6 men, 2 women) healthy older (65-75 yr old) subjects. BP and HR were measured using an automated device and SMA blood flow was measured using Doppler ultrasound on 4 days in random order. SMA blood flow was calculated using the radius of the SMA and time-averaged mean velocity. Subjects were intubated with a nasoduodenal catheter incorporating a duodenal infusion port. On 2 of the 4 days, they were intubated orally with a second catheter, incorporating a barostat bag, positioned in the fundus and set at 8 mmHg above minimal distending pressure. Each subject received a 60-min (0-60 min) intraduodenal infusion of glucose (3 kcal/min) or saline (0.9%); therefore, the four study conditions were as follows: intraduodenal glucose + barostat (glucose + distension), intraduodenal saline + barostat (saline + distension), intraduodenal glucose (glucose), and intraduodenal saline (saline). Systolic and diastolic BP fell during glucose compared with saline (P = 0.05 and P = 0.003, respectively) and glucose + distension (P = 0.01 and P = 0.05, respectively) and increased during saline + distension compared with saline (P = 0.04 and P = 0.006, respectively). The maximum changes in systolic BP were -14 +/- 5, +11 +/- 2, -3 +/- 4, and +15 +/- 3 mmHg for glucose, saline, glucose + distension, and saline + distension, respectively. There was an increase in HR during glucose and glucose + distension (maximum rise = 14 +/- 2 and 14 +/- 3 beats/min, respectively), but not during saline or saline + distension. SMA blood flow increased during glucose and glucose + distension (2,388 +/- 365 and 1,673 +/- 187 ml/min, respectively), but not during saline, and tended to decrease during saline + distension (821 +/- 115 and 864 +/- 116 ml/min, respectively). In conclusion, gastric distension has the capacity to abolish the fall in BP and attenuate the rise in SMA blood flow induced by intraduodenal glucose in healthy older subjects.

Comparative effects of oral and intraduodenal glucose on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects.

Postprandial hypotension occurs frequently, particularly in the elderly. The magnitude of the fall in blood pressure (BP) and rise in heart rate (HR) in response to enteral glucose are greater when gastric emptying (GE) or small intestinal infusion are more rapid. Meal ingestion is associated with an increase in splanchnic blood flow. In contrast, gastric distension may attenuate the postprandial fall in BP. The aims of this study were to evaluate, in older subjects, the comparative effects of intraduodenal glucose infusion, at a rate similar to GE of oral glucose, on BP, HR, superior mesenteric artery (SMA) flow, and blood glucose. Eight healthy subjects (5 men, 3 women, age 66-75 yr) were studied on two occasions. On day 1, each subject ingested 300 ml of water containing 75 g glucose. GE was quantified by three-dimensional ultrasonography between time t = 0-120 min, and the rate of emptying (kcal/min) was calculated. On day 2, glucose was infused intraduodenally at the same rate as that on day 1. On both days, BP, HR, SMA flow, and blood glucose were measured. The mean GE of oral glucose was 1.3 +/- 0.1 kcal/min. Systolic BP (P < 0.01), SMA flow (P < 0.05), and blood glucose (P < 0.01) were greater and HR less (P < 0.01) after oral, compared with intraduodenal, glucose. There were comparable falls in diastolic BP during the study days (P < 0.01 for both). We conclude that the magnitude of the fall in systolic BP and rise in HR are less after oral, compared with intraduodenal, glucose, presumably reflecting the "protective" effect of gastric distension.

Effects of intraduodenal glucose, fat, and protein on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects.

BACKGROUND: Postprandial hypotension frequently occurs in the elderly. The hypotensive response to a meal is triggered by the interaction of nutrients with the small intestine; information relating to the effects of different macronutrients on blood pressure (BP) is limited and inconsistent. OBJECTIVE: The objective of the study was to determine the effects of intraduodenal glucose, fat, and protein on BP, heart rate (HR), and superior mesenteric artery (SMA) blood flow in healthy older subjects. DESIGN: Eight subjects received intraduodenal glucose (64 g), fat (10% oil emulsion), protein (72 g whey), or saline (0.9%) at a rate of 2.7 mL/min for 90 min, followed by intraduodenal saline for 30 min. BP, HR, and SMA blood flow were measured. RESULTS: The falls in systolic BP during infusions of glucose, fat, and protein did not differ significantly (P=0.97); however, the fall occurred significantly earlier during the glucose infusion; (18+/-3.0 min) than during the fat (46+/-11.0 min; P=0.02) and protein 33+/-7 min; P=0.04) infusions. The increases in HR during glucose, fat, and protein infusions (P<0.0001 for all) did not differ significantly. SMA blood flow increased significantly after all infusions (P<0.001 for all), but the increase was significantly (P<0.05) lower after protein than after the other infusions. CONCLUSIONS: Intraduodenal glucose, fat, and protein decrease systolic BP in healthy older subjects, but the onset of the hypotensive response is earlier after glucose, and the effect of protein on SMA blood flow is less than that of the other nutrients.

Effects of mid-jejunal compared to duodenal glucose infusion on peptide hormone release and appetite in healthy men.

INTRODUCTION: Cells containing GIP and CCK predominate in the upper small intestine, while those containing GLP-1 are located more distally. Our aim was to compare the hormonal, glycemic and appetite responses to different sites of glucose delivery. METHODS: Ten healthy males were each studied twice, in randomized order. A catheter was positioned with openings 15 cm beyond the pylorus ("duodenal"), and 100 cm beyond ("mid-jejunal"). On one day, glucose was infused into the duodenum (1 kcal/min) and saline into the mid-jejunum, for 90 min. On the other day, the infusion sites were reversed. Blood was sampled frequently, and hunger was scored by questionnaires. The tube was removed and energy intake measured from a buffet meal. RESULTS: Stimulation of CCK and suppression of hunger were greater (each P<0.05), and energy intake less (P=0.05), with duodenal compared to mid-jejunal glucose infusion. Blood glucose, GIP, and insulin did not differ, and there was minimal GLP-1 increment on either day. CONCLUSIONS: There is regional variation in CCK, but not incretin hormone release, in the upper small intestine, and modest differences in the site of glucose exposure affect appetite and energy intake.

Transient, early release of glucagon-like peptide-1 during low rates of intraduodenal glucose delivery.

CONTEXT: The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1. OBJECTIVE: To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response. DESIGN: Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min. SETTING: Clinical research laboratory. PARTICIPANTS: 27 healthy subjects (24 male; age 36+/-3 years; BMI 25.2+/-0.7 kg/m(2)). MAIN OUTCOME MEASURES: Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM. RESULTS: During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P<0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P<0.001), insulin (P<0.001), and blood glucose (P<0.001). CONCLUSION: In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.

Intravenous CCK-8, but not GLP-1, suppresses ghrelin and stimulates PYY release in healthy men.

We have investigated the effects of exogenous CCK-8 and GLP-1, alone and in combination, on ghrelin and PYY secretion. Nine healthy males were studied on four occasions. Plasma ghrelin and PYY concentrations were measured during 150 min intravenous infusions of: (i) isotonic saline, (ii) CCK-8 at 1.8 pmol/kg/min, (iii) GLP-1 at 0.9 pmol/kg/min or (iv) CCK-8 and GLP-1 combined. CCK-8 markedly suppressed ghrelin and stimulated PYY when compared with control between t=0-120 min (P<0.001 for both). GLP-1 had no effect on ghrelin, but decreased PYY slightly at 120 min (P<0.05). During infusion of CCK-8+GLP-1, there was comparable suppression of ghrelin (P<0.001), but the stimulation of PYY was less (P<0.001), than that induced by CCK-8, between t=20-120 min. In conclusion, in healthy subjects, in the doses evaluated, exogenous CCK-8 suppresses ghrelin and stimulates PYY, and exogenous GLP-1 has no effect on ghrelin and attenuates the effect of CCK-8 on PYY.

Effect of fatty acid chain length on suppression of ghrelin and stimulation of PYY, GLP-2 and PP secretion in healthy men.

We have evaluated the effects of fatty acid chain length on ghrelin, peptide YY (PYY), glucagon-like peptide-2 (GLP-2) and pancreatic polypeptide (PP) secretion and hypothesized that intraduodenal administration of dodecanoic ("C12"), but not decanoic ("C10"), acid would decrease plasma ghrelin and increase PYY, GLP-2 and PP concentrations. Plasma hormone concentrations were measured in seven healthy men during 90-min intraduodenal infusions of: (i) C12, (ii) C10 or (iii) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10) and after a buffet-meal consumed following the infusion. C12 markedly suppressed plasma ghrelin and increased both PYY and GLP-2 (all P < 0.05) compared with control and C10, while C10 had no effect. Both C10 and C12 increased PP concentrations slightly (P < 0.05). We conclude that the effects of intraduodenal fatty acids on ghrelin, PYY and GLP-2 secretion are dependent on their chain length.

Humanitarian assistance in Afghanistan: a prospective evaluation of clinical effectiveness.

OBJECTIVE: To examine the clinical effectiveness of patient encounters during humanitarian assistance (HA) missions performed by the 48th Combat Support Hospital in Afghanistan. METHODS: Data were prospectively gathered from missions in the villages of Aroki (January 21, 2003), Tangee (March 25, 2003), and Turkman (April 22, 2003). Health care providers evaluated the effectiveness of each patient encounter using a data-gathering instrument with clearly defined outcome measures. RESULTS: A total of 1,887 patients were seen during the three missions. Forms were incomplete for 112 patients and not used for 33 dental patients. For the remaining 1,742 individuals, probable cures were achieved as follows: adult males, 31%; adult females, 52%; male children, 46%; and female children, 54% (all patients, 46%, p < 0.001). After adjusting for acute care that was supportive in nature during the final mission, probable cures were achieved as follows: adult males, 22%; adult females, 16%; male children, 34%; and female children, 27%. During this final operation, 73% (p < 0.001) of patients received care that was unnecessary, unlikely to produce a cure, or was merely supportive in nature. CONCLUSIONS: During HA missions performed by the 48th Combat Support Hospital, the majority of patient encounters did not result in curative treatments. The effectiveness of medical care during HA missions cannot be assumed and future operations should include assessments of outcomes to optimize their value.

Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes.

The determinants of postprandial blood glycemia are controversial. We assessed the effects of variations in the initial rate of small intestinal glucose delivery on blood glucose, plasma insulin, and incretin responses in both health and type 2 diabetes. Eight controls and eight patients with type 2 diabetes managed by diet alone underwent paired studies. On both days subjects received an intraduodenal glucose infusion (t = 0-120 min); on one day the infusion rate was variable, being more rapid initially (3 kcal/min) between t = 0 and 15 min and slower (0.71 kcal/min) subsequently (t = 15-120 min), whereas on the other day, the infusion rate was constant (1 kcal/min) from t = 0 to 120 min (i.e. on both days 120 kcal of glucose were administered). Between t = 0-180 min blood glucose, plasma insulin and plasma glucose-dependent insulin-releasing polypeptide were greater with the variable, compared with the constant, infusion. Between t = 0 and 30 min the magnitude of the rise in plasma glucagon-like peptide-1 was greater with the variable, compared with the constant infusion (P < 0.01, both groups). We conclude that modest variations in the initial rate of duodenal glucose entry may have profound effects on subsequent glycemic, insulin, and incretin responses.

Effects of intraluminal local anesthetic on upper gastrointestinal motor, sensory, and peptide hormone responses to intraduodenal glucose.

OBJECTIVE: Enterally administered glucose modifies gut sensation, diminishes hunger, and slows gastric emptying by suppressing antral motility and stimulating pyloric pressures. We aimed to clarify the mechanism of small intestinal glucose sensing. METHODS: We studied eight healthy males twice, in random order. An antroduodenal manometry catheter was positioned with a sleeve sensor across the pylorus. Benzocaine, or vehicle alone, was given into the proximal duodenum as a bolus, followed by continuous infusion for 105 min (T=-15 to 90 min). Glucose was also infused into the proximal duodenum at 3 kcal/min for 90 min (T=0-90 min). Sensations of hunger, bloating, and nausea were assessed with visual analog questionnaires, blood was sampled at intervals, and energy intake at a buffet meal (T=90-120 min) was measured. RESULTS: Perceptions of bloating and nausea were markedly less with benzocaine when compared with vehicle (P<0.05 for each), with no difference in hunger, or energy intake. In contrast, the suppression of antral waves and stimulation of phasic and tonic pyloric pressures, duodenal waves, and propagated duodenal wave sequences by intraduodenal glucose infusion did not differ between the 2 days. No difference in blood glucose, plasma insulin, or plasma glucagon-like peptide 1 between benzocaine and control was observed, whereas glucose-dependent insulinotropic polypeptide and cholecystokinin concentrations were slightly higher with benzocaine (P<0.05 for both). CONCLUSION: Mucosal anesthesia ameliorates unpleasant sensations induced by enteral glucose, but does not inhibit the release of gut peptides that feed back on appetite and gastroduodenal motility.

Effects of varying combinations of intraduodenal lipid and carbohydrate on antropyloroduodenal motility, hormone release, and appetite in healthy males.

Intraduodenal infusions of both lipid and glucose modulate antropyloroduodenal motility and stimulate plasma CCK, with lipid being more potent than glucose. Both stimulate glucagon-like peptide-1, but only lipid stimulates peptide YY (PYY), while only glucose raises blood glucose and stimulates insulin. When administered in combination, lipid and carbohydrate may, thus, have additive effects on energy intake. However, elevated blood glucose levels do not suppress energy intake, and the effect of insulin is controversial. We hypothesized that increasing the ratio of maltodextrin, a complex carbohydrate, relative to lipid would be associated with a reduction in effects on antropyloroduodenal pressures, gut hormones, appetite, and energy intake, when compared with lipid alone. Ten healthy males were studied on three occasions in double-blind, randomized order. Antropyloroduodenal pressures, plasma CCK, PYY and insulin, blood glucose, and appetite were measured during 90-min intraduodenal infusions of 1) 3 kcal/min lipid (L3), 2) 2 kcal/min lipid and 1 kcal/min maltodextrin (L2/CHO1), or 3) 1 kcal/min lipid and 2 kcal/min maltodextrin (L1/CHO2). Energy intake at a buffet lunch consumed immediately after the infusion was quantified. Reducing the lipid (thus, increasing the carbohydrate) content of the infusion was associated with reduced stimulation of basal pyloric pressures (r = 0.76, P < 0.01), plasma CCK (r = 0.66, P < 0.01), and PYY (r = 0.98, P < 0.001), and reduced suppression of antral (r = -0.64, P < 0.05) and duodenal (r = -0.69, P < 0.05) pressure waves, desire-to-eat (r = -0.8, P < 0.001), and energy intake (r = 0.74, P < 0.01), with no differences in phasic (isolated) pyloric pressures. In conclusion, in healthy males, intraduodenal lipid is a more potent modulator of gut function, associated with greater suppression of energy intake, when compared with isocaloric combinations of lipid and maltodextrin.

Comparative effects of intraduodenal infusions of lauric and oleic acids on antropyloroduodenal motility, plasma cholecystokinin and peptide YY, appetite, and energy intake in healthy men.

BACKGROUND: The regulation of gastrointestinal function and energy intake by fatty acids depends on their chain length. Animal studies suggest that lauric acid (C12) may have more potent suppressive effects on energy intake than does oleic acid (C18). OBJECTIVE: We compared the effects of equicaloric loads of C12 and C18 on antropyloroduodenal (APD) motility, plasma concentrations of cholecystokinin (CCK) and peptide YY (PYY), appetite, and energy intake. DESIGN: Thirteen healthy men (aged 20-46 y) were studied on 3 occasions in double-blind, randomized fashion. APD pressure waves, plasma hormones, and appetite perceptions were measured during 60-min intraduodenal infusions of 1) C12, 2) C18, or 3) 0.9% saline as control (rate: 4 mL/min; energy load for C12 and C18: 0.4 kcal/min); between 60 and 90 min, the subjects consumed a meal. Energy intake at a buffet meal was quantified. RESULTS: C12 and C18 both reduced antral (P < 0.001) and duodenal (P < 0.01) pressure waves and stimulated isolated pyloric pressure waves (P < 0.01) and plasma CCK (P < 0.001), with no differences between them. Although C12 and C18 both increased basal pyloric pressure (P < 0.05), C12 had a greater effect than did C18 (P < 0.01). In contrast, although both C12 and C18 increased plasma PYY (P < 0.001), C18 had a greater effect than C12. C12, but not C18, suppressed energy intake (P < 0.05). CONCLUSIONS: At the load administered, C12, but not C18, suppressed energy intake, and C12 was a more potent stimulant of basal pyloric pressure. These discrepant effects are not apparently accounted for by changes in CCK or PYY secretion.

Gastric distension attenuates the hypotensive effect of intraduodenal glucose in healthy older subjects.

Postprandial hypotension occurs frequently, and current management is suboptimal. Recent studies suggest that the magnitude of the fall in postprandial blood pressure (BP) may be attenuated by gastric distension. The aim of this study was to determine the effect of gastric distension on the hypotensive response to intraduodenal (ID) glucose. Eight healthy subjects (5 males, 3 females, aged 65-76 years) received an ID infusion of either 1) 50 g glucose in 300 ml saline (ID glucose) over 60 min (t=0-60 min), 2) 50 g glucose in 300 ml saline over 60 min and intragastric (4) infusion of 500 ml water between t=7-10 min (IG water and ID glucose), or 3) ID saline (0.9%) infusion over 60 min and IG infusion of 500 ml water (IG water and ID saline) all followed by ID saline infusion for another 60 min (t=60-120 min) on three separate days. BP and heart rate (HR) were measured. Gastric emptying (GE) of the IG water was quantified by two-dimensional ultrasonography. Between t=0-60 min, systolic and diastolic BP was greater (P<0.05 for both) with IG water and ID saline compared with IG water and ID glucose, and less (P<0.05 for both) with ID glucose compared with IG water and ID glucose. These effects were evident at relatively low IG volumes (approximately 300 ml). GE was faster with IG water and ID saline when compared with IG water and ID glucose. We conclude that, in healthy older subjects, IG administration of water markedly attenuates the hypotensive response to ID glucose, presumably as a result of gastric distension.

A high-fat diet raises fasting plasma CCK but does not affect upper gut motility, PYY, and ghrelin, or energy intake during CCK-8 infusion in lean men.

There is evidence from studies in animals that the effects of both fat and CCK on gastrointestinal function and energy intake are attenuated by consumption of a high-fat diet. In humans, the effects of exogenous CCK-8 on antropyloroduodenal motility, plasma CCK, peptide YY (PYY), and ghrelin concentrations, appetite, and energy intake are attenuated by a high-fat diet. Ten healthy lean males consumed isocaloric diets (~15,400 kJ per day), containing either 44% (high-fat, HF) or 9% (low-fat, LF) fat, for 21 days in single-blind, randomized, cross-over fashion. Immediately following each diet (i.e., on day 22), subjects received a 45-min intravenous infusion of CCK-8 (2 ng.kg(-1).min(-1)), and effects on antropyloroduodenal motility, plasma CCK, PYY, ghrelin concentrations, hunger, and fullness were determined. Thirty minutes after commencement of the infusion, subjects were offered a buffet-style meal, from which energy intake (in kilojoules) was quantified. Body weight was unaffected by the diets. Fasting CCK (P < 0.05), but not PYY and ghrelin, concentrations were greater following the HF, compared with the LF, diet. Infusion of CCK-8 stimulated pyloric pressures (P < 0.01) and suppressed antral and duodenal pressures (P < 0.05), with no difference between the diets. Energy intake also did not differ between the diets. Short-term consumption of a HF diet increases fasting plasma CCK concentrations but does not affect upper gut motility, PYY and ghrelin, or energy intake during CCK-8 infusion, in a dose of 2 ng.kg(-1).min(-1), in healthy males.

Load-dependent effects of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men.

Both load and duration of small intestinal lipid infusion affect antropyloroduodenal motility and CCK and peptide YY (PYY) release at loads comparable to and higher than the normal gastric emptying rate. We determined 1) the effects of intraduodenal lipid loads well below the mean rate of gastric emptying on, and 2) the relationships between antropyloroduodenal motility, CCK, PYY, appetite, and energy intake. Sixteen healthy males were studied on four occasions in double-blind, randomized fashion. Antropyloroduodenal motility, plasma CCK and PYY, and appetite perceptions were measured during 50-min IL (Intralipid) infusions at: 0.25 (IL0.25), 1.5 (IL1.5), and 4 (IL4) kcal/min or saline (control), after which energy intake at a buffet meal was quantified. IL0.25 stimulated isolated pyloric pressure waves (PWs) and CCK release, albeit transiently, and suppressed antral PWs, PW sequences, and hunger (P < 0.05) but had no effect on basal pyloric pressure or PYY when compared with control. Loads >/= 1.5 kcal/min were required for the stimulation of basal pyloric pressures and PYY and suppression of duodenal PWs (P < 0.05). All of these effects were related to the lipid load (R > 0.5 or < -0.5, P < 0.05). Only IL4 reduced energy intake (in kcal: control, 1,289 +/- 62; IL0.25, 1,282 +/- 44; IL1.5, 1,235 +/- 71; and IL4, 1,139 +/- 65 compared with control and IL0.25, P < 0.05). In conclusion, in healthy males the effects of intraduodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, appetite, and energy intake are load dependent, and the threshold loads required to elicit responses vary for these parameters.

Effects of lauric acid on upper gut motility, plasma cholecystokinin and peptide YY, and energy intake are load, but not concentration, dependent in humans.

Animal studies suggest that the effects of fatty acids on gastric emptying and pancreatic secretion are both concentration and load dependent, while their suppressive effect on energy intake is only load dependent. We postulated that, in humans, the modulation of antropyloroduodenal pressure waves, plasma cholecystokinin (CCK) and peptide YY (PYY) concentrations and energy intake by intraduodenal lauric acid, a fatty acid with 12 carbon atoms ('C12') would be load, but not concentration, dependent. Two groups of 12 healthy males were each studied on three separate occasions in double-blind randomized fashion. Antropyloroduodenal pressure waves, plasma CCK and PYY, and appetite perceptions were measured during intraduodenal infusions of C12 at (1) different loads of (i) 0.2, (ii) 0.3 and (iii) 0.4 kcal min(-1) (all 56 mM) for 90 min, and (2) different concentrations of (i) 40, (ii) 56 and (iii) 72 mM (all 0.4 kcal min(-1)) for 60 min. Energy intake at a buffet meal consumed immediately following each infusion was quantified. Suppression of antral and duodenal pressure waves, stimulation of pyloric pressure waves, stimulation of plasma CCK and PYY, and suppression of energy intake, were related to the load of C12 administered (r>0.65, P<0.05). In contrast, there were no concentration-dependent effects of C12 on any of these parameters. In conclusion, in humans, the effects of intraduodenal C12 on antropyloroduodenal motility, plasma CCK and PYY and energy intake appear to be related to load, but not concentration, at least at the loads and concentrations evaluated.

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

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.

Free fatty acids have more potent effects on gastric emptying, gut hormones, and appetite than triacylglycerides.

BACKGROUND & AIMS: The effects of fat on gastric emptying (GE), gut hormones, and energy intake are dependent on digestion to free fatty acids (FFAs). In animals, small intestinal oleic acid inhibits energy intake more potently than the triacylglyceride (TG) triolein, but there is limited information about the comparative effects of FFA and TG in human beings. We compared the effects of FFA and TG on GE, gut hormone secretion, appetite, and energy intake in healthy males. METHODS: Nine men (age, 23 +/- 2 y; body mass index, 22 +/- 1 kg/m(2)) were studied on 3 occasions to evaluate the effects of (1) 40 g oleic acid (FFA, 1830 kJ), (2) 40 g macadamia oil (TG, 1856 kJ; both 600-mL oil-in-water emulsions stabilized with 4% milk protein and labeled with 15 MBq (123)I), or (3) 600 mL 4% milk protein (control, 352 kJ), administered intragastrically, on GE, plasma cholecystokinin (CCK) and peptide-YY (PYY) levels, appetite perceptions, and subsequent energy intake. RESULTS: GE of FFA was much slower than that of TG (P < .05), with greater retention of FFA, than TG, in the proximal stomach (P < .001). Hunger was less (P < .05), and fullness was greater (P < .05), after FFA when compared with control and TG. Increases in plasma CCK and PYY levels were greater after FFA than TG or control (P < .05). Energy intake tended to be less after FFA compared with TG (control, 4754 +/- 610 kJ; TG, 5463 +/- 662 kJ; FFA, 4199 +/- 410 kJ). CONCLUSIONS: FFAs empty from the stomach more slowly, but stimulate CCK and PYY and suppress appetite more potently than TG in healthy human beings.

Effects of intraduodenal glucose concentration on blood pressure and heart rate in healthy older subjects.

The aims of this study were to determine whether the hypotensive and heart rate responses to small intestinal glucose infusion are dependent on the glucose concentration. Eight healthy subjects, aged 65-78 years, were studied on 3 separate days in random order. Each subject received intraduodenal infusions of 50 g of glucose in either 300 mL (16.7%), 600 mL (8.3%), or 1200 mL (4.1%) of saline (0.9%) at a rate of 3 kcal/min for 60 minutes (t = 0-60 minutes), followed by saline (0.9%) for a further 60 minutes (t = 60-120 minutes). During the infusions, blood pressure (systolic and diastolic) and heart rate were measured every 3 minutes, and blood glucose concentrations every 15 minutes. Systolic and diastolic blood pressure fell (P < .0001), and heart rate and blood glucose increased (P = .0001 for both) over time, during all 3 infusions. Between t = -2-120 minutes, there was no difference in systolic blood pressure (P = .20), diastolic blood pressure (P = .61), or heart rate (P = .09) over the study days. There was also no significant difference in the glycemic response to the infusions. We conclude that in healthy older subjects, glucose concentration does not affect the blood pressure or heart rate responses to intraduodenal glucose and that, therefore, the magnitude of the postprandial fall in blood pressure induced by oral glucose is likely to depend primarily on the small intestinal glucose load.

Effects of load, and duration, of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men.

Enterally administered lipid modulates antropyloroduodenal motility, gut hormone release, appetite, and energy intake. We hypothesized that these effects would be dependent on both the load, and duration, of small intestinal exposure to lipid. Eleven healthy men were studied on four occasions in a double-blind, randomized, fashion. Antropyloroduodenal motility, plasma CCK and peptide YY (PYY) concentrations, and appetite perceptions were measured during intraduodenal infusion of lipid (Intralipid) at 1) 1.33 kcal/min for 50 min, 2) 4 kcal/min for 50 min, and 3) 1.33 kcal/min for 150 min, or 4) saline for 150 min. Immediately after the infusions, energy intake was quantified. Pressure wave sequences (PWSs) were suppressed, and basal pyloric pressure, isolated pyloric pressure waves (IPPWs), plasma CCK and PYY stimulated (all P < 0.05), during the first 50 min of lipid infusion, in a load-dependent fashion. The effect of the 4 kcal/min infusion was sustained so that the suppression of antral pressure waves (PWs) and PWSs and increase in PYY remained evident after cessation of the infusion (all P < 0.05). The prolonged lipid infusion (1.33 kcal/min for 150 min) suppressed antral PWs, stimulated CCK and PYY and basal pyloric pressure (all P < 0.05), and tended to stimulate IPPWs when compared with saline throughout the entire infusion period. There was no significant effect of any of the lipid infusions on appetite or energy intake, although nausea was slightly higher (P < 0.05) with the 4 kcal/min infusion. In conclusion, both the load, and duration, of small intestinal lipid influence antropyloroduodenal motility and patterns of CCK and PYY release.