RESUMEN
AIMS: Liraglutide reduces bodyweight in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the mechanisms underlying this effect. METHODS: The comparative effects of liraglutide, glimepiride and placebo on energy intake, appetite, nausea, gastric emptying, antral distension, bodyweight, gastrointestinal hormones, fasting plasma glucose and resting energy expenditure (REE), were assessed in subjects with T2DM randomised to treatment A (liraglutide-placebo), B (placebo-glimepiride) or C (glimepiride-liraglutide). Assessments were performed at the end of each 4-week treatment period. RESULTS: Energy intake was less (NS) with liraglutide vs placebo and glimepiride, and 24-h REE was higher (NS) with liraglutide vs placebo and glimepiride. Fasting hunger was less (p=0.01) with liraglutide vs placebo and glimepiride, and meal duration was shorter with liraglutide (p=0.002) vs placebo. Paracetamol AUC(0-60 min) and C(max) were less (p<0.01) and fasting peptide YY was lower (p ≤ 0.001) after liraglutide vs placebo and glimepiride. Bodyweight reductions of 1.3 and 2.0 kg were observed with liraglutide vs placebo and glimepiride (p<0.001). There were no differences on antral distension, nausea, or other gastro-intestinal hormones. CONCLUSION: Liraglutide caused decreased gastric emptying and increased reduction in bodyweight. The mechanisms of the liraglutide-induced weight-loss may involve a combined effect on energy intake and energy expenditure.
Asunto(s)
Apetito/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ingestión de Energía/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Vaciamiento Gástrico/efectos de los fármacos , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/administración & dosificación , Obesidad/tratamiento farmacológico , Compuestos de Sulfonilurea/administración & dosificación , Adolescente , Adulto , Anciano , Australia , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Péptido 1 Similar al Glucagón/farmacología , Humanos , Hipoglucemiantes/administración & dosificación , Liraglutida , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Obesidad/fisiopatología , Compuestos de Sulfonilurea/farmacología , Adulto JovenRESUMEN
Gastric emptying (GE) of glucose is regulated closely, not only as a result of inhibitory feedback arising from the small intestine, but also because of the resulting hyperglycemia. Fructose is used widely in the diabetic diet and is known to empty from the stomach slightly faster than glucose but substantially slower than water. The aims of this study were to determine whether intravenous (iv) fructose affects GE and antropyloroduodenal motility and how any effects compare to those induced by iv glucose. Six healthy males (age: 26.7 +/- 3.8 yr) underwent concurrent measurements of GE of a solid meal (100 g ground beef labeled with 20 MBq (99m)Tc-sulfur colloid) and antropyloroduodenal motility on three separate days in randomized order during iv infusion of either fructose (0.5 g/kg), glucose (0.5 g/kg), or isotonic saline for 20 min. GE (scintigraphy), antropyloroduodenal motility (manometry), and blood glucose (glucometer) were measured for 120 min. There was a rise in blood glucose (P < 0.001) after iv glucose (peak 16.4 +/- 0.6 mmol/l) but not after fructose or saline. Intravenous glucose and fructose both slowed GE substantially (P < 0.005 for both), without any significant difference between them. Between t = 0 and 30 min, the number of antral pressure waves was less after both glucose and fructose (P < 0.002 for both) than saline, and there were more isolated pyloric pressure waves during iv glucose (P = 0.003) compared with fructose and saline (P = NS for both) infusions. In conclusion, iv fructose slows GE and modulates gastric motility in healthy subjects, and the magnitude of slowing of GE is comparable to that induced by iv glucose.
Asunto(s)
Duodeno/efectos de los fármacos , Fructosa/administración & dosificación , Vaciamiento Gástrico/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Glucosa/administración & dosificación , Estómago/efectos de los fármacos , Adulto , Glucemia/efectos de los fármacos , Duodeno/diagnóstico por imagen , Duodeno/fisiología , Humanos , Infusiones Intravenosas , Masculino , Manometría , Presión , Cintigrafía , Radiofármacos , Método Simple Ciego , Estómago/diagnóstico por imagen , Estómago/fisiología , Azufre Coloidal Tecnecio Tc 99m , Adulto JovenRESUMEN
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.
Asunto(s)
Apetito/fisiología , Duodeno/metabolismo , Glucosa/metabolismo , Yeyuno/metabolismo , Hormonas Peptídicas/metabolismo , Adulto , Apetito/efectos de los fármacos , Glucemia/análisis , Colecistoquinina/sangre , Duodeno/efectos de los fármacos , Duodeno/fisiología , Ingestión de Energía/efectos de los fármacos , Ingestión de Energía/fisiología , Polipéptido Inhibidor Gástrico/sangre , Péptido 1 Similar al Glucagón/sangre , Glucosa/administración & dosificación , Glucosa/farmacología , Humanos , Hambre/fisiología , Insulina/sangre , Yeyuno/efectos de los fármacos , Yeyuno/fisiología , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: Dietary interventions represent a promising therapeutic strategy to optimize postprandial glycemia. The addition of protein to oral glucose has been reported to improve the glycemic profile. OBJECTIVE: The aim of the current study was to evaluate the mechanisms by which protein supplementation lowers the blood glucose response to oral glucose. DESIGN: Nine healthy men were studied on 3 d each in a random order. Subjects consumed 300-mL drinks containing either 50 g glucose (Glucose), 30 g gelatin (Protein), or 50 g glucose with 30 g gelatin (Glucose + Protein) in water labeled with 150 mg [(13)C]acetate. Blood and breath samples were subsequently collected for 3 h to measure blood glucose and plasma insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations and gastric half-emptying time, which was calculated from (13)CO(2) excretion. RESULTS: The blood glucose response was less after Glucose + Protein than after Glucose (P < 0.005); GIP was lower (P < 0.005), and there were no significant differences in plasma insulin or GLP-1. Protein alone stimulated insulin, GLP-1, and GIP (P < 0.05 for each) without elevating blood glucose. The gastric half-emptying time was greater after Glucose + Protein than after Glucose (P < 0.05) and tended to be greater for Glucose than for Protein (P = 0.06). CONCLUSIONS: In healthy humans, the addition of protein to oral glucose lowers postprandial blood glucose concentrations acutely, predominantly by slowing gastric emptying, although protein also stimulates incretin hormones and non-glucose-dependent insulin release.
Asunto(s)
Glucemia/análisis , Proteínas en la Dieta/administración & dosificación , Vaciamiento Gástrico , Glucosa/administración & dosificación , Incretinas/sangre , Administración Oral , Adulto , Péptido 1 Similar al Glucagón/sangre , Humanos , Insulina/sangre , MasculinoRESUMEN
OBJECTIVE: We previously reported that a single preprandial injection (120 microg) of pramlintide, an analog of the beta-cell hormone amylin, reduced ad libitum food intake in obese subjects. To further characterize the meal-related effects of amylin signaling in humans, we studied a lower pramlintide dose (30 microg) in normal-weight subjects. RESEARCH METHODS AND PROCEDURES: In a randomized, double-blind, placebo-controlled, cross-over study, 15 healthy men (age, 24 +/- 7 years; BMI, 22.2 +/- 1.8 kg/m(2)) underwent a standardized buffet meal test on two occasions. After an overnight fast, subjects received a single subcutaneous injection of pramlintide (30 microg) or placebo, followed immediately by a standardized pre-load meal. After 1 hour, subjects were offered an ad libitum buffet meal, and total caloric intake and meal duration were measured. RESULTS: Compared with placebo, pramlintide reduced total caloric intake (1411 +/- 94 vs. 1190 +/- 117 kcal; Delta, -221 +/- 101 kcal; -14 +/- 9%; p = 0.05) and meal duration (36 +/- 2 vs. 31 +/- 3 minutes; Delta, -5.1 +/- 1.4 minutes; p < 0.005). Visual analog scale profiles of hunger trended lower and fullness higher during the first hour after pramlintide administration. In response to the buffet, hunger and fullness changed to a similar degree after pramlintide and placebo, despite subjects on pramlintide consuming 14% fewer kilocalories. Visual analog scale nausea ratings remained near baseline, without differences between treatments. Plasma peptide YY, cholecystokinin, and ghrelin concentrations did not differ with treatment, whereas glucagon-like peptide-1 concentrations after meals were lower in response to pramlintide than to placebo. DISCUSSION: These observations add support to the concept that amylin agonism may have a role in human appetite control.
Asunto(s)
Amiloide/farmacología , Ingestión de Alimentos/fisiología , Ingestión de Energía/efectos de los fármacos , Adulto , Anciano , Índice de Masa Corporal , Peso Corporal , Estudios Cruzados , Método Doble Ciego , Humanos , Hipoglucemiantes/farmacología , Polipéptido Amiloide de los Islotes Pancreáticos , Masculino , Persona de Mediana Edad , Placebos , Periodo Posprandial , Valores de Referencia , Factores de TiempoRESUMEN
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.
Asunto(s)
Bromuro de Butilescopolamonio/farmacología , Duodeno/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón/sangre , Glucosa/metabolismo , Absorción Intestinal/efectos de los fármacos , Antagonistas Muscarínicos/farmacología , 3-O-Metilglucosa/sangre , 3-O-Metilglucosa/metabolismo , Adulto , Glucemia/efectos de los fármacos , Estudios de Casos y Controles , Duodeno/inervación , Duodeno/metabolismo , Impedancia Eléctrica , Polipéptido Inhibidor Gástrico , Tránsito Gastrointestinal/efectos de los fármacos , Humanos , Insulina/sangre , Masculino , Manometría/métodos , Peristaltismo/efectos de los fármacos , Valores de Referencia , Sensibilidad y Especificidad , Método Simple Ciego , Factores de TiempoRESUMEN
BACKGROUND: Mixed alcoholic drinks are increasingly being consumed in "diet" varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with "regular" versions containing sugar. METHODS: We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage (30 g ethanol in 600 mL), made with either "regular" mixer containing sucrose (total 478 kcal), or "diet" mixer (225 kcal). RESULTS: Gastric half-emptying time measured by ultrasound (mean+/-standard deviation) was less for the "diet" than the "regular" drink (21.1+/-9.5 vs 36.3+/-15.3 minutes, P <.01). Both the peak blood ethanol concentration (0.053+/-0.006 vs 0.034+/-0.008 g%, P <.001) and the area under the blood ethanol concentration curve between 0 and 180 minutes (5.2+/-0.7 vs 3.2+/-0.7 units, P <.001) were greater with the "diet" drink. CONCLUSIONS: Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.
Asunto(s)
Bebidas/análisis , Etanol/metabolismo , Vaciamiento Gástrico/efectos de los fármacos , Sacarosa/farmacología , Edulcorantes/farmacología , Absorción/efectos de los fármacos , Adulto , Estudios Cruzados , Método Doble Ciego , Etanol/sangre , Humanos , Masculino , Sacarosa/química , Edulcorantes/químicaRESUMEN
Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1 and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age 18-59 yr) over 60 min on the first day into an isolated 60-cm segment of the proximal small intestine ("short-segment infusion"); on the second day, the same amount of glucose was infused with access to the entire small intestine ("long-segment infusion"). Plasma GLP-1 increased and ghrelin decreased (P < 0.05 for both) during the long-, but not the short-, segment infusion. By contrast, increases in plasma CCK and GIP did not differ between days. The rises in blood glucose and plasma insulin were greater during the long- than during the short-segment infusion (P < 0.05). During the long- but not the short-segment infusion, antral pressure waves (PWs) were suppressed (P < 0.05). Isolated pyloric PWs and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon >60 cm of the intestine being exposed to glucose.
Asunto(s)
Colecistoquinina/sangre , Polipéptido Inhibidor Gástrico/sangre , Péptido 1 Similar al Glucagón/sangre , Glucosa/farmacología , Intestino Delgado/fisiología , Hormonas Peptídicas/sangre , Adolescente , Adulto , Glucemia/efectos de los fármacos , Ghrelina , Glucosa/administración & dosificación , Glucosa/farmacocinética , Humanos , Insulina/sangre , Absorción Intestinal/fisiología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Intubación Gastrointestinal , Masculino , Persona de Mediana Edad , Presión , Antro Pilórico/fisiología , Píloro/fisiología , Método Simple CiegoRESUMEN
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.
Asunto(s)
Glucemia/análisis , Glucosa/administración & dosificación , Frecuencia Cardíaca/fisiología , Hipotensión/diagnóstico , Factores de Edad , Anciano , Análisis de Varianza , Determinación de la Presión Sanguínea , Femenino , Evaluación Geriátrica , Humanos , Hipotensión/sangre , Infusiones Intravenosas , Masculino , Periodo Posprandial , Probabilidad , Estudios Prospectivos , Valores de Referencia , Medición de RiesgoRESUMEN
The rate of gastric emptying of glucose-containing liquids is a major determinant of postprandial glycemia. The latter is also dependent on stimulation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Although overall emptying of glucose approximates 1-3 kcal/min, the "early phase" of gastric emptying is usually more rapid. We have evaluated the hypothesis that increased stimulation of incretin hormones and insulin by a more rapid initial rate of small intestinal glucose delivery would reduce the overall glycemic response to a standardized enteral glucose load. Twelve healthy subjects were studied on two separate days in which they received an intraduodenal (id) glucose infusion for 120 min. On one day, the infusion rate was variable, being more rapid (6 kcal/min) between t = 0 and 10 min and slower (0.55 kcal/min) between t = 10 and 120 min, whereas on the other day the rate was constant (1 kcal/min) from t = 0-120 min, i.e., on both days 120 kcal were given. Between t = 0 and 75 min, plasma insulin, GIP, and GLP-1 were higher with the variable infusion. Despite the increase in insulin and incretin hormones, blood glucose levels were also higher. Between t = 75 and 180 min, blood glucose and plasma insulin were lower with the variable infusion. There was no difference in the area under the curve 0-180 min for blood glucose. We conclude that stimulation of incretin hormone and insulin release by a more rapid initial rate of id glucose delivery does not lead to an overall reduction in glycemia in healthy subjects.
Asunto(s)
Polipéptido Inhibidor Gástrico/sangre , Glucagón/sangre , Glucosa/farmacocinética , Hiperglucemia/prevención & control , Insulina/sangre , Intestino Delgado/metabolismo , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Vaciamiento Gástrico , Péptido 1 Similar al Glucagón , Humanos , Hiperglucemia/metabolismo , Masculino , Periodo Posprandial , Valores de ReferenciaRESUMEN
OBJECTIVE: Ghrelin is a peptide hormone secreted primarily from the gastric mucosa. It plays a role in energy balance by stimulating appetite, thereby increasing food intake and enhancing weight gain and fat mass deposition. Plasma ghrelin concentrations increase with fasting and are suppressed by nutrient intake. The aim of this study was to examine in humans the relative contributions of small intestinal and gastric nutrient exposure to postprandial suppression of ghrelin, to determine whether gastric exposure is necessary for ghrelin suppression. PATIENTS: Twelve healthy older (age range 65-85 years) men (n = 7) and women (n = 5) were studied. DESIGN: On three separate days, equivolaemic (315 ml) intragastric (IG) and intraduodenal (ID) carbohydrate solutions (both 300 kcal) or intragastric water (control) were infused over 150 min. MEASUREMENTS: Food intake was quantified at a buffet meal offered immediately following each 150-min infusion. Blood ghrelin, cholecystokinin and glucose concentrations were measured. RESULTS: There was a 25% suppression of mean plasma ghrelin concentrations following ID glucose (ID 2016 vs. control 2686 ng/l, P < 0.0001) and a 19% suppression following IG glucose (IG 2181 vs. control 2686 ng/l, P < 0.0001), with ghrelin concentrations slightly (7.6%) and nonsignificantly lower after ID than after IG glucose infusions (P = 0.2). There was no difference between the treatments for the amount of food consumed at the buffet meal (P = 0.88). CONCLUSIONS: Although the primary source of ghrelin is the gastric mucosa, these results suggest that small intestinal nutrient exposure is sufficient for food-induced plasma ghrelin suppression in humans, and that gastric nutrient exposure is not necessary for suppression.
Asunto(s)
Duodeno/metabolismo , Ingestión de Energía/efectos de los fármacos , Mucosa Gástrica/metabolismo , Glucosa , Hormonas Peptídicas/sangre , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Apetito/efectos de los fármacos , Glucemia/análisis , Colecistoquinina/sangre , Depresión Química , Esquema de Medicación , Duodeno/efectos de los fármacos , Femenino , Ghrelina , Humanos , Absorción Intestinal , Masculino , Estómago/efectos de los fármacosRESUMEN
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.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/metabolismo , Polipéptido Inhibidor Gástrico/sangre , Glucagón/sangre , Glucosa/farmacocinética , Insulina/sangre , Intestino Delgado/metabolismo , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Disponibilidad Biológica , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/dietoterapia , Duodeno , Femenino , Péptido 1 Similar al Glucagón , Glucosa/administración & dosificación , Humanos , Persona de Mediana Edad , Concentración OsmolarRESUMEN
The presence of nutrients in the small intestine slows gastric emptying and suppresses appetite and food intake; these effects are partly mediated by the release of gut hormones, including CCK. We investigated the hypothesis that the modulation of antropyloroduodenal motility, suppression of appetite, and stimulation of CCK and glucagon-like peptide-1 secretion by intraduodenal fat are dependent on triglyceride hydrolysis by lipase. Sixteen healthy, young, lean men were studied twice in double-blind, randomized, crossover fashion. Ratings for appetite-related sensations, antropyloroduodenal motility, and plasma CCK and glucagon-like peptide-1 concentrations were measured during a 120-min duodenal infusion of a triglyceride emulsion (2.8 kcal/min) on one day with, on the other day without, 120 mg tetrahydrolipstatin, a potent lipase inhibitor. Immediately after the duodenal fat infusion, food intake at a buffet lunch was quantified. Lipase inhibition with tetrahydrolipstatin was associated with reductions in tonic and phasic pyloric pressures, increased numbers of isolated antral and duodenal pressure waves, and stimulation of antropyloroduodenal pressure-wave sequences (all P < 0.05). Scores for prospective consumption and food intake at lunch were greater, and nausea scores were slightly less, and the rises in plasma CCK and glucagon-like peptide-1 were abolished (all P < 0.05). In conclusion, lipase inhibition attenuates the effects of duodenal fat on antropyloroduodenal motility, appetite, and CCK and glucagon-like peptide-1 secretion.
Asunto(s)
Apetito/efectos de los fármacos , Colecistoquinina/metabolismo , Grasas de la Dieta/metabolismo , Grasas de la Dieta/farmacología , Duodeno/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Glucagón/metabolismo , Fragmentos de Péptidos/metabolismo , Precursores de Proteínas/metabolismo , Adulto , Colecistoquinina/sangre , Estudios Cruzados , Grasas de la Dieta/administración & dosificación , Método Doble Ciego , Glucagón/sangre , Péptido 1 Similar al Glucagón , Humanos , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Masculino , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
OBJECTIVES: Corticotropin-releasing factor (CRF) has been shown to affect GI motor function and appetite in animals. We have evaluated the effects of exogenous CRF on antropyloroduodenal motility and appetite in humans. METHODS: On 2 separate days, six healthy volunteers received, in randomized, double-blind fashion, i.v. CRF as a 1.0-microg/kg bolus (0-5 min) followed by a constant infusion (1.0 microg/kg/h) (5-150 min), or an identical volume of saline. At t = 28 min each subject drank 200 ml of a nutrient liquid containing 20 mg/kg of paracetamol. Antropyloroduodenal pressures were measured with sleeve/sidehole manometry and perceptions of appetite by visual analog scales. Venous blood was obtained for measurements of serum cortisol and paracetamol. At t = 150 min the manometric catheter was removed and subjects offered a buffet meal (150-180 min). The amount and macronutrient content of food consumed were quantified. RESULTS: CRF increased serum cortisol (p < 0.001), the number of isolated pyloric pressure waves (p < 0.05), duodenal pressure waves (p < 0.05), and the percentage of antegrade duodenal pressure waves (p < 0.05). CRF had no significant effect on the number of antral pressure waves, basal pyloric pressure, serum paracetamol concentrations, perceptions of appetite, or food intake. CONCLUSIONS: Intravenous CRF stimulates phasic pyloric and duodenal pressure waves in humans.