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Introduction: Hyperbaric oxygen (HBO2) improves outcome in patients with acute carbon monoxide (CO) poisoning, but optimal dose/timing are unknown. In this double-blind, sham-controlled randomized trial, we compared neuropsychological sequelae at six weeks and six months in patients receiving three HBO2 sessions or one HBO2 session and two sham chamber sessions after acute CO poisoning. Methods: After completing one HBO2 session (3.0 ATA, 60 minutes, 2.0 ATA, 65 minutes), CO-poisoned patients were randomized (1:1): two sham chamber sessions (1 ATA air, 120 minutes) or two additional HBO2sessions (2.0 ATA, 90 minutes at pressure, 120 minutes in chamber) completed within 24 hours. Eligible patients were >24 hours from accidental poisoning, English-speaking, and not intubated. We planned 150 participants. Results: The study was stopped early for enrollment futility. From 2006 to 2016, we screened 395 patients: 136 were deemed eligible to participate, and 75 signed informed consent. Two were later withdrawn for past brain injury/PTSD (one sham, one HBO2), and one for performance validity (sham). Of the 72 analyzed, mean age was 42 ± 15 years, 40 (56%) were male, 20 (28%) had loss of consciousness, and mean initial carboxyhemoglobin was 22 ± 9%. The rate of six-week neuropsychological sequelae was 50% in the one-HBO2 session group and 55% in the three-HBO2 sessions group (p = 0.80), and at six months was 42% versus 46%, respectively (p = 0.76). Conclusions: There was no difference in the rate of neuropsychological sequelae in those who received three HBO2 sessions and those who received one HBO2 sessions and two sham sessions. The higher rate of neuropsychological sequelae compared to an earlier study may be due to neuropsychological test-retest effects or previously identified risk factors for cognitive sequelae (age, duration of poisoning, cerebellar dysfunction). This study's rates of cognitive difficulties, affective complaints, and other symptoms suggest brain injury after CO poisoning is common.
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Developmental DNA elimination in Paramecium tetraurelia occurs through a trans-nuclear comparison of the genomes of two distinct types of nuclei: the germline micronucleus (MIC) and the somatic macronucleus (MAC). During sexual reproduction, which starts with meiosis of the germline nuclei, MIC-limited sequences including Internal Eliminated Sequences (IESs) and transposons are eliminated from the developing MAC in a process guided by noncoding RNAs (scnRNAs and iesRNAs). However, our current understanding of this mechanism is still very limited. Therefore, studying both genetic and epigenetic aspects of these processes is a crucial step to understand this phenomenon in more detail. Here, we describe the involvement of homologs of classical meiotic proteins, Spo11, Msh4-1, and Msh5 in this phenomenon. Based on our analyses, we propose that proper functioning of Spo11, Msh4-1, and Msh5 during Paramecium sexual reproduction are necessary for genome reorganization and viable progeny. Also, we show that double-strand breaks (DSBs) in DNA induced during meiosis by Spo11 are crucial for proper IESs excision. In summary, our investigations show that early sexual reproduction processes may significantly influence later somatic genome integrity.
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Paramecium tetraurelia , Células Germinativas , Macronúcleo/genética , Macronúcleo/metabolismo , Meiosis/genética , Paramecium tetraurelia/genética , Paramecium tetraurelia/metabolismo , ARN no Traducido/metabolismoRESUMEN
In eukaryotic cells, about one-third of the synthesized proteins are translocated into the endoplasmic reticulum; they are membrane or lumen resident proteins and proteins direct to the Golgi apparatus. The co-translational translocation takes place through the heterotrimeric protein-conducting channel Sec61 which is associated with the ribosome and many accessory components, such as the heterotetrameric translocon-associated protein (TRAP) complex. Recently, microscopic techniques, such as cryo-electron microscopy and cryo-electron tomography, have enabled the determination of the translocation machinery structure. However, at present, there is a lack of understanding regarding the roles of some of its components; indeed, the TRAP complex function during co-translational translocation needs to be established. In addition, TRAP may play a role during unfolded protein response, endoplasmic-reticulum-associated protein degradation and congenital disorder of glycosylation (ssr4 CDG). In this article, I describe the current understanding of the TRAP complex in the light of its possible function(s).
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Proteínas de Unión al Calcio/química , Proteínas de Unión al Calcio/metabolismo , Retículo Endoplásmico/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Péptidos/química , Receptores de Péptidos/metabolismo , Animales , Microscopía por Crioelectrón , Aparato de Golgi/metabolismo , Humanos , Modelos Moleculares , Transporte de Proteínas , Proteolisis , Respuesta de Proteína DesplegadaRESUMEN
OBJECTIVE: Some practitioners advocate hyperbaric oxygen (HBO2) for sequelae following brain injury. This study assessed recruitment, tolerance and safety in preparation for a randomized clinical trial. DESIGN: Prospective, open-label feasibility study. SETTING: Hyperbaric medicine department of a tertiary academic hospital. PARTICIPANTS: Participatory adult outpatients with problems from stroke (n=22), anoxia (13) or trauma (28) that occurred at least 12 months before enrollment, without contraindications to HBO2. Sixty-three participants enrolled in the study (21 females,42 males). Age was 45 +/- 16 years (18-76) and time from injury was 6.9 +/- 7.1 years (1.0-29.3). Fifty-three completed the study intervention, and 55 completed the assessment battery. METHODS: PARTICIPANTS underwent 60 daily HBO2 sessions (1.5 atm abs, 100% oxygen, 60 minutes). Assessments were conducted at baseline, after the HBO2 course, and six months later. MAIN OUTCOME MEASUREMENTS: The prime outcome was feasibility. To estimate the immediate and long-term effects of HBO2, we assessed neuropsychological measures, questionnaires, neurologic exam and physical functioning measures. Some participants also had pre- and post-HBO2 speech evaluation (n=27) and neuroimaging (n=17). RESULTS: The study met our a priori definition for feasibility for recruitment, but 44% required additional time to complete the 60 sessions (up to 105 days). HBO2-related adverse events were rare and not serious. Although many participants reported improvement in symptoms (51% memory, 51% attention/concentration, 48% balance/coordination, 45% endurance, 20% sleep) post-HBO2, and 93% reported that they would participate in the study again, no standardized testing showed clinically important improvement. In the small subset of those undergoing neuroimaging, apparent improvement was observed in auditory functional MRI (8/13), MR spectroscopy (9/17) and brain perfusionby CT angiography (5/9). CONCLUSIONS: Conducting an HBO2 clinical trial in this population was feasible. Although many participants reported improvement, the lack of concurrent controls limits the strength of inferences from this trial, especially considering lack of change in standardized testing. The clinical relevance of neuroimaging changes is unknown. The findings of this study may indicate a need for caution when considering the broad application of HBO2 more than one year after brain injury due to stroke, severe TBI and anoxia, until there is more compelling evidence from carefully designed sham-controlled, blinded clinical trials.
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Daño Encefálico Crónico/terapia , Lesiones Encefálicas/complicaciones , Oxigenoterapia Hiperbárica/métodos , Hipoxia Encefálica/complicaciones , Accidente Cerebrovascular/complicaciones , Adolescente , Adulto , Anciano , Análisis de Varianza , Daño Encefálico Crónico/etiología , Angiografía Cerebral/métodos , Estudios de Factibilidad , Femenino , Humanos , Oxigenoterapia Hiperbárica/efectos adversos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen Neurológico , Seguridad del Paciente , Selección de Paciente , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Observations relating to the impact of obesity on gastric emptying (GE) and the secretion of gut hormones are inconsistent, probably because of a lack of studies in which GE, gastrointestinal hormone release, and energy intake (EI) have been evaluated concurrently with previous patterns of nutrient intake. GE is known to be a major determinant of postprandial glycemia and incretin secretion in health and type 2 diabetes. The aims of this study were to determine the effects of a mixed-nutrient drink on GE, oro-cecal transit, blood glucose, insulin and incretin concentrations and EI, and the relationship between the glycemic response to the drink with GE in lean, overweight, and obese subjects. Twenty lean, 20 overweight, and 20 obese males had measurements of GE, oro-cecal transit, and blood glucose, insulin, GLP-1, and GIP concentrations for 5 h after ingestion of a mixed-nutrient drink (500 ml, 532 kcal); EI at a subsequent buffet lunch was determined. Habitual EI was also quantified. Glycemic and insulinemic responses to the drink were greater in the obese (both P < 0.05) when compared with both lean and overweight, with no significant differences in GE, intragastric distribution, oro-cecal transit, incretins, or EI (buffet lunch or habitual) between groups. The magnitude of the rise in blood glucose after the drink was greater when GE was relatively more rapid (r = -0.55, P < 0.05). In conclusion, in the absence of differences in habitual EI, both GE and incretin hormones are unaffected in the obese despite greater glucose and insulin responses, and GE is a determinant of postprandial glycemia.
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Ingestión de Energía , Vaciamiento Gástrico , Tránsito Gastrointestinal , Incretinas/metabolismo , Insulina/sangre , Sobrepeso/fisiopatología , Delgadez/fisiopatología , Adulto , Índice Glucémico , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To evaluate the natural history of gastric emptying in diabetes. RESEARCH DESIGN AND METHODS: Thirteen patients with diabetes (12, type 1; 1, type 2) had measurements of gastric emptying, blood glucose levels, glycated hemoglobin, upper gastrointestinal symptoms, and autonomic nerve function at baseline and after 24.7 ± 1.5 years. RESULTS: There was no change in gastric emptying of either solids (% retention at 100 min) (baseline 58.5 ± 5% vs. follow-up 51.9 ± 8%; P = 0.35) or liquids (50% emptying time) (baseline 29.8 ± 3 min vs. follow-up 34.3 ± 6 min; P = 0.37). Gastric emptying of solid at follow-up was related to emptying at baseline (r = 0.56, P < 0.05). At follow-up, blood glucose concentrations were lower (P = 0.006), autonomic function deteriorated (P = 0.03), and gastrointestinal symptoms remained unchanged (P = 0.17). CONCLUSIONS: In unselected patients with diabetes, gastric emptying appears remarkably stable over 25 years.
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Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Vaciamiento Gástrico/fisiología , Anciano , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana EdadRESUMEN
CONTEXT: Postprandial hyperglycemia is an important clinical problem in cystic fibrosis (CF), but the contribution of fat malabsorption, rapid gastric emptying, and the incretin axis has not been widely considered. OBJECTIVE: The aim of this study was to evaluate these aspects of gut function in nondiabetic CF patients. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled crossover study at a clinical research laboratory. PATIENTS: Five nondiabetic CF patients (three males; age, 25.8 ± 1.0 yr; body mass index, 20.2 ± 1.1 kg/m(2)) with exocrine pancreatic insufficiency and six healthy subjects of similar age and body mass index participated in the study. INTERVENTIONS: CF patients consumed a radiolabeled mashed potato meal on 2 separate days, together with four capsules of Creon Forte (100,000 IU lipase) or placebo. Healthy subjects consumed the meal once, without pancreatic enzymes. MAIN OUTCOME MEASURES: Gastric emptying was measured using scintigraphy, and blood was sampled frequently for blood glucose and plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon concentrations. RESULTS: CF patients had more rapid gastric emptying (P < 0.001), impaired secretion of GLP-1 (P < 0.01) and GIP (P < 0.001), and greater postprandial glycemic excursions (P < 0.001) than healthy subjects. Pancreatic enzyme supplementation normalized gastric emptying and GLP-1 secretion and tended to increase glucagon (P = 0.08), but did not completely restore GIP secretion or normalize postprandial blood glucose. There was an excellent correlation between gastric emptying and blood glucose concentration at 60 min (R = 0.75; P = 0.01). CONCLUSIONS: Pancreatic enzyme supplementation plays an important role in incretin secretion, gastric emptying, and postprandial hyperglycemia in CF.
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Glucemia/metabolismo , Fibrosis Quística/fisiopatología , Vaciamiento Gástrico/fisiología , Hiperglucemia/metabolismo , Incretinas/metabolismo , Lipasa/uso terapéutico , Páncreas/enzimología , Adulto , Fibrosis Quística/sangre , Carbohidratos de la Dieta/farmacología , Grasas de la Dieta/farmacología , Método Doble Ciego , Femenino , Polipéptido Inhibidor Gástrico/sangre , Glucagón/sangre , Péptido 1 Similar al Glucagón/sangre , Humanos , Insulina/sangre , Masculino , 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.
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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: Delayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients. METHODS: Studies were performed in nineteen mechanically-ventilated critically ill patients and compared to nineteen healthy subjects. Following 4 hours fasting, 100 ml of Ensure, 2 g 3-O-methyl glucose (3-OMG) and 99mTc sulphur colloid were infused into the stomach over 5 minutes. Glucose absorption (plasma 3-OMG), blood glucose levels and GE (scintigraphy) were measured over four hours. Data are mean +/- SEM. A P-value < 0.05 was considered significant. RESULTS: Absorption of 3-OMG was markedly reduced in patients (AUC240: 26.2 +/- 18.4 vs. 66.6 +/- 16.8; P < 0.001; peak: 0.17 +/- 0.12 vs. 0.37 +/- 0.098 mMol/l; P < 0.001; time to peak; 151 +/- 84 vs. 89 +/- 33 minutes; P = 0.007); and both the baseline (8.0 +/- 2.1 vs. 5.6 +/- 0.23 mMol/l; P < 0.001) and peak (10.0 +/- 2.2 vs. 7.7 +/- 0.2 mMol/l; P < 0.001) blood glucose levels were higher in patients; compared to healthy subjects. In patients; 3-OMG absorption was directly related to GE (AUC240; r = -0.77 to -0.87; P < 0.001; peak concentrations; r = -0.75 to -0.81; P = 0.001; time to peak; r = 0.89-0.94; P < 0.001); but when GE was normal (percent retention240 < 10%; n = 9) absorption was still impaired. GE was inversely related to baseline blood glucose, such that elevated levels were associated with slower GE (ret 60, 180 and 240 minutes: r > 0.51; P < 0.05). CONCLUSIONS: In critically ill patients; (i) the rate and extent of glucose absorption are markedly reduced; (ii) GE is a major determinant of the rate of absorption, but does not fully account for the extent of impaired absorption; (iii) blood glucose concentration could be one of a number of factors affecting GE.
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Glucemia/metabolismo , Enfermedad Crítica , Vaciamiento Gástrico/fisiología , Guanosina/análogos & derivados , Absorción Intestinal/fisiología , Adulto , Anciano , Sacarosa en la Dieta/administración & dosificación , Sacarosa en la Dieta/metabolismo , Nutrición Enteral , Femenino , Alimentos Formulados , Índice Glucémico , Guanosina/administración & dosificación , Guanosina/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Azufre Coloidal Tecnecio Tc 99m/administración & dosificaciónRESUMEN
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.
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Depresores del Apetito/farmacología , Apetito/efectos de los fármacos , Ácidos Grasos no Esterificados/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Hormonas Gastrointestinales/sangre , Tracto Gastrointestinal/efectos de los fármacos , Ácido Oléico/farmacología , Aceites de Plantas/farmacología , Triglicéridos/farmacología , Administración Oral , Adulto , Depresores del Apetito/administración & dosificación , Bebidas , Colecistoquinina/sangre , Método Doble Ciego , Ingestión de Energía/efectos de los fármacos , Ácidos Grasos no Esterificados/administración & dosificación , Tracto Gastrointestinal/metabolismo , Tránsito Gastrointestinal/efectos de los fármacos , Humanos , Macadamia/química , Masculino , Proteínas de la Leche/administración & dosificación , Ácido Oléico/administración & dosificación , Péptido YY/sangre , Aceites de Plantas/administración & dosificación , Aceites de Plantas/aislamiento & purificación , Valores de Referencia , Factores de Tiempo , Triglicéridos/administración & dosificación , Triglicéridos/aislamiento & purificaciónRESUMEN
OBJECTIVE: The herbal preparation Iberogast has been reported to improve upper abdominal symptoms in functional dyspepsia (FD) and to decrease fundic tone, increase antral contractility, and decrease afferent nerve sensitivity in experimental animals. The effects of Iberogast on the human gastrointestinal tract have not been evaluated. METHODS: We investigated the effects of oral control and Iberogast, each administered as a single dose (1.1 mL), in a double-blind randomized fashion, on proximal gastric volume (part A), antropyloroduodenal motility (part B), and gastric emptying and intragastric distribution of a solid/liquid meal (part C) for 120 minutes, in nine (part A), 12 (part B), and eight (part C) healthy men. RESULTS: Iberogast increased proximal gastric volume (max volume; control 104+/-12 mL, Iberogast 174+/-23 mL, P<0.05) (part A), increased the motility index of antral pressure waves in the first 60 minutes (P<0.05) without affecting pyloric or duodenal pressures (part B), and slightly increased the retention of liquid in the total stomach between 10 and 50 minutes (P<0.01), but had no effect on gastric emptying of solids or intragastric distribution (part C). CONCLUSIONS: Iberogast affects gastric motility in humans, probably in a region-dependent manner. The stimulation of gastric relaxation and antral motility may contribute to the reported therapeutic efficacy of Iberogast in FD.
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Vaciamiento Gástrico/efectos de los fármacos , Motilidad Gastrointestinal/efectos de los fármacos , Extractos Vegetales/farmacología , Estómago/efectos de los fármacos , Adulto , Método Doble Ciego , Humanos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Estómago/fisiologíaRESUMEN
The rate of alcohol absorption is dependent on gastric emptying (GE). As the slowing of GE by fat is dependent on lipolysis, orlistat may increase the rise in blood alcohol when alcohol is consumed with, or after, fat. The aim of the study was to evaluate the effects of orlistat on GE and blood alcohol after an alcohol-containing drink following a fat 'preload', in healthy subjects. Ten healthy males consumed 120 ml cream with or without 120 mg orlistat, 30 min before an alcohol-containing drink labelled with 20 MBq [(99 m)Tc]sulfur colloid on 2 d. GE, plasma alcohol and blood glucose were measured. GE was slightly faster with orlistat (P<0.05) compared with control. Plasma alcohol at 15 min was slightly higher with orlistat (0.034 (SEM 0.006) g/100 ml) v. control (0.029 (SEM 0.005) g/100 ml) (P<0.05), but there was no effect on the area under the curve 0-240 min. The increase in blood glucose was greater with orlistat, for example, at 15 min (1.07 (SEM 0.2) mmol/l) v. control (0.75 (SEM 0.2) mmol/l) (P=0.05). The rise in blood glucose and plasma alcohol were related (for example, at 15 min r 0.49; P=0.03). In conclusion, lipase inhibition accelerates GE of an alcohol-containing drink following a fat 'preload' with a minor increase in the initial rise in plasma alcohol.
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Inhibidores Enzimáticos/administración & dosificación , Etanol/farmacocinética , Vaciamiento Gástrico/fisiología , Lactonas/administración & dosificación , Lipasa/antagonistas & inhibidores , Absorción , Adulto , Área Bajo la Curva , Bebidas , Glucemia/análisis , Etanol/administración & dosificación , Etanol/sangre , Humanos , Masculino , Orlistat , Método Simple CiegoRESUMEN
Previous studies suggest that posture has relatively little effect on gastric emptying of high-nutrient liquids; these studies have, however, only assessed overall rates of gastric emptying, whereas gastric emptying is known to be predominantly a pulsatile phenomenon. In healthy subjects perceptions of appetite, such as hunger, are inversely related to antral area and content; hence, changes in intragastric meal distribution induced by posture may affect appetite. Gastric emptying is a major determinant of postprandial glycemia. The aims of this study were to evaluate the effects of posture on patterns of transpyloric flow (TF), gastric emptying (GE), antral area (AA), hunger, and the glycemic response to oral glucose. Eight healthy young subjects (five males, three females; mean age, 24.0 +/- 2.4 years; BMI, 21.2 +/- 0.6 kg/m2) were studied twice in random order, once in the sitting position and once in the lying (supine) position. After consuming 600 ml water with 75 g glucose, labeled with 20 MBq 99mTc-sulfur colloid, subjects had simultaneous measurements of (i) TF during consumption of the drink by Doppler ultrasonography, (ii) GE with scintigraphy, (iii) AA at t = -5 and t = 30 min by ultrasonography, and (iv) perceptions of appetite with a visual analogue scale. During drink ingestion TF was greater in the sitting, compared with the lying, position (586 +/- 170 vs. 177 +/- 65 [cm/sec] x sec; P < 0.05). Posture affected intragastric distribution; more of the drink was retained in the distal stomach in the sitting position (e.g., at 30 min: sitting, 29 +/- 3%, vs. lying, 12 +/- 3%; P < 0.0001) but had no effect on the overall rate of GE or the blood glucose response. AA at t = 30 min (P < 0.005) was greater in the sitting position; there was an inverse relationship between hunger and AA at 30 min (r = -0.53, P < 0.05). We conclude that posture influences initial TF and intragastric distribution, but not the overall rate of GE of, or the glycemic response to, a large-volume nutrient liquid. The increases in AA and content in the sitting position are associated with a reduction in hunger.
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Vaciamiento Gástrico/fisiología , Glucosa/administración & dosificación , Hambre/fisiología , Postura/fisiología , Píloro/fisiología , Edulcorantes/administración & dosificación , Administración Oral , Adulto , Glucemia/metabolismo , Femenino , Estudios de Seguimiento , Glucosa/farmacocinética , Humanos , Masculino , Antro Pilórico/diagnóstico por imagen , Antro Pilórico/fisiología , Píloro/diagnóstico por imagen , Valores de Referencia , Edulcorantes/farmacocinética , UltrasonografíaRESUMEN
CONTEXT: Gastric emptying (GE) is a major determinant of postprandial glycemia. Because the presence of fat in the small intestine inhibits GE, ingestion of fat may attenuate the glycemic response to carbohydrate. OBJECTIVE: The objective of this study was to evaluate the effect of patterns of fat consumption on GE and glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations after a carbohydrate meal in type 2 diabetes. DESIGN: This was a randomized, cross-over study in which GE of a radioisotopically labeled potato meal was measured on 3 d. SETTING: The study was performed at the Royal Adelaide Hospital. PATIENTS: Six males with type 2 diabetes were studied. INTERVENTION: Subjects ingested 1) 30 ml water 30 min before the mashed potato (water), 2) 30 ml olive oil 30 min before the mashed potato (oil), or 3) 30 ml water 30 min before the mashed potato meal that contained 30 ml olive oil (water and oil). MAIN OUTCOME MEASURES: GE, blood glucose, plasma insulin, GLP-1, and GIP concentrations were the main outcome measures. RESULTS: GE was much slower with oil compared with both water (P < 0.0001) and water and oil (P < 0.05) and was slower after water and oil compared with water (P < 0.01). The postprandial rise in blood glucose was markedly delayed (P = 0.03), and peak glucose occurred later (P = 0.04) with oil compared with the two other meals. The rises in insulin and GIP were attenuated (P < 0.0001), whereas the GLP-1 response was greater (P = 0.0001), after oil. CONCLUSIONS: Ingestion of fat before a carbohydrate meal markedly slows GE and attenuates the postprandial rises in glucose, insulin, and GIP, but stimulates GLP-1, in type 2 diabetes.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Vaciamiento Gástrico , Polipéptido Inhibidor Gástrico/sangre , Péptido 1 Similar al Glucagón/sangre , Insulina/sangre , Anciano , Estudios Cruzados , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Gastric emptying (GE) of a solid (100 g beef) and liquid (150 ml 10 % dextrose) meal was measured in eight patients with type 1 diabetes during intravenous infusion of C-peptide (6 pmol/kg/ min) or isotonic saline. C-peptide had no effect on either solid or liquid GE.
Asunto(s)
Péptido C/farmacología , Diabetes Mellitus Tipo 1/fisiopatología , Vaciamiento Gástrico/efectos de los fármacos , Adulto , Glucemia/análisis , Péptido C/sangre , Diabetes Mellitus Tipo 1/sangre , Femenino , Vaciamiento Gástrico/fisiología , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
CONTEXT: The inhibitory action of glucagon-like peptide-1 (GLP-1) on gastric emptying (GE) is likely to be important in mediating its effects on postprandial glycemia, appetite, and gastrointestinal symptoms. OBJECTIVE: The objective of the study was to evaluate the effects of "low" and "high" doses of iv GLP-1 on GE, intragastric meal distribution, glycemia, insulinemia, and appetite. DESIGN: Ten healthy males were studied on 3 d. GE of a solid (ground beef)/liquid (glucose) meal, blood glucose, plasma insulin, glucagon and glucose-dependent insulinotropic peptide, appetite perceptions, and gastrointestinal symptoms were evaluated during iv infusion of: 1) GLP-1 at 0.3 pmol x kg(-1) x min(-1) (GLP-1 0.3); 2) GLP-1 at 0.9 pmol x kg(-1) x min(-1) (GLP-1 0.9); and 3) 0.9% saline. RESULTS: GLP-1 0.3 and 0.9 slowed GE of solid (intragastric retention at t = 100 min; saline: 28 +/- 5%; GLP-1 0.3: 53 +/- 6%; GLP-1 0.9: 58 +/- 7%; P < 0.001) and liquid (time for 50% of the liquid to empty, saline: 28 +/- 2 min; GLP-1 0.3: 42 +/- 7 min; GLP-1 0.9: 50 +/- 9 min; P < 0.001). Both doses of GLP-1 induced gastroparesis in about half the cohort and increased meal retention in the distal stomach (P < 0.05). GLP-1 attenuated the rises in glucose, insulin, and glucose-dependent insulinotropic peptide (P < 0.05). There was an inverse relationship between blood glucose at t = 15 min and the time for 50% of the liquid to empty (r = -0.70, P < 0.001). CONCLUSIONS: In healthy subjects exogenous GLP-1 increases meal retention in the distal stomach and, even when administered in a "low" dose, frequently induces "gastroparesis," and the effects of GLP-1 on postprandial glycemia are predictable on the basis of its effect on GE, supporting the concept that GE is a major target mechanism for the clinical use of incretin mimetics.
Asunto(s)
Glucemia/metabolismo , Vaciamiento Gástrico/efectos de los fármacos , Mucosa Gástrica/metabolismo , Péptido 1 Similar al Glucagón/farmacología , Insulina/sangre , Periodo Posprandial/efectos de los fármacos , Adulto , Apetito/fisiología , Polipéptido Inhibidor Gástrico/sangre , Glucagón/sangre , Péptido 1 Similar al Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/farmacocinética , Humanos , Hambre/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Respuesta de Saciedad/efectos de los fármacos , Estómago/efectos de los fármacos , Resultado del TratamientoRESUMEN
CONTEXT: The rate of gastric emptying of carbohydrate is a major determinant of postprandial glycemia. In healthy subjects and patients with uncomplicated type 1 diabetes, there is evidence that gastric emptying may be accelerated by insulin-induced hypoglycemia. OBJECTIVE: The objective was to determine the effects of acute hypoglycemia on gastric emptying in long-standing type 1 diabetes and evaluate whether the response to hypoglycemia is influenced by the rate of gastric emptying during euglycemia and/or autonomic dysfunction. DESIGN: Gastric emptying of a solid/liquid meal (100 g (99m)Tc-minced beef and 150 ml 67Ga-EDTA-labeled water) was measured by scintigraphy on 2 separate days, during hypoglycemia and euglycemia. SETTING: These studies took place at the Department of Nuclear Medicine, Positron Emission Tomography, and Bone Densitometry at the Royal Adelaide Hospital. PATIENTS: Twenty type 1 patients (4 female, 16 male; age, 45.9 +/- 2.3 yr; duration of known diabetes, 18.0 +/- 2.7 yr) were recruited from outpatient clinics and the Diabetes Centre at the Royal Adelaide Hospital. INTERVENTION: Hypoglycemia (approximately 2.6 mmol/liter) was established 15 min before and maintained for 45 min after meal consumption. On one of the days, autonomic nerve function was evaluated using cardiovascular reflex tests. MAIN OUTCOME MEASURE: The main outcome measure was gastric emptying during hypoglycemia when compared with euglycemia. RESULTS: Twelve of the 20 subjects had autonomic neuropathy. Gastric emptying of both solid (P < 0.001) and liquid (P < 0.05) was faster during hypoglycemia. The magnitude of this acceleration was greater when the rate of gastric emptying during euglycemia was slower (solid, percentage retention at 100 min, r = -0.52, P < 0.05; liquid, 50% emptying time, r = -0.82, P < 0.0001, but not influenced by autonomic nerve function). CONCLUSIONS: Insulin-induced hypoglycemia accelerates gastric emptying of solids and liquids in long-standing type 1 diabetes, even in those patients with delayed emptying, and is likely to be an important mechanism in the counter-regulation of hypoglycemia.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Vaciamiento Gástrico/fisiología , Hipoglucemia/fisiopatología , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Adulto , Presión Sanguínea , Ingestión de Líquidos , Ingestión de Alimentos , Femenino , Radioisótopos de Galio , Vaciamiento Gástrico/efectos de los fármacos , Técnica de Clampeo de la Glucosa , Frecuencia Cardíaca , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/etiología , Masculino , Persona de Mediana Edad , TecnecioRESUMEN
The aims of this study were to evaluate (i) the relationship between transpyloric flow (TF) assessed by Doppler ultrasonography and scintigraphy, (ii) the effects of healthy aging on TF and gastric emptying (GE), and (iii) the relationship between the glycemic response to oral glucose and TF. Ten healthy "young" (7 M, 3 F) and 8 "older" (4 M, 4 F), subjects had simultaneous measurements of TF, GE, and blood glucose after a 600-ml drink (75 g glucose labeled with 20 MBq 99mTc-sulfur colloid) while seated. TF measured by ultrasound was measured during drink ingestion and for 30 min thereafter. GE was measured scintigraphically for 180 min after drink ingestion. Blood glucose was measured before the drink and at regular intervals until 180 min. During drink ingestion, TF was greater (P < 0.05) and GE faster (retention at 60 min: 70.8+/-3.3 vs. 83.8+/-4.6%; P < 0.05) in young compared to older subjects. There was no difference in fasting blood glucose between the two groups but the magnitude of the rise in blood glucose was greater in the young compared to the older subjects; (at 15 min 2.4+/-0.3 vs. 1.5+/-0.5 mmol/L; P < 0.05). In contrast, after 90 min blood glucose concentrations were higher in the older subjects. There were significant relationships between the early blood glucose concentration and both TF (e.g., at 15 min: r = 0.56, P < 0.05) and GE (e.g., at 15 min: r = -0.51, P < 0.05). In conclusion, the results of this study indicate that (i) TF is initially less, and GE slower, in older compared to young subjects; (ii) the initial glycemic response to oral glucose is related to TF; and (iii) measurements of TF by ultrasound and scintigraphy correlate significantly.
Asunto(s)
Envejecimiento/fisiología , Glucemia/metabolismo , Vaciamiento Gástrico , Píloro/fisiología , Administración Oral , Adulto , Anciano , Ingestión de Líquidos , Femenino , Glucosa/administración & dosificación , Glucosa/farmacología , Humanos , Masculino , Concentración Osmolar , Píloro/diagnóstico por imagen , Cintigrafía , Valores de Referencia , Azufre Coloidal Tecnecio Tc 99m , Factores de Tiempo , Ultrasonografía DopplerRESUMEN
Postprandial hypotension (PPH) occurs frequently in the elderly; the magnitude of the fall in blood pressure (BP) is related to the rate of glucose entry into the duodenum during intraduodenal glucose infusion and spontaneous gastric emptying (GE). It is unclear if glucose concentration affects the hypotensive response. Gastric distension may attenuate PPH; therefore, meal volume could influence the BP response. We aimed to determine the effects of 1) drink volume, 2) glucose concentration, and 3) glucose content on the BP and heart rate (HR) responses to oral glucose. Ten subjects (73.9 +/- 1.2 yr) had measurements of BP, GE, and blood glucose on 4 days after 1) 25 g glucose in 200 ml (12.5%), 2) 75 g glucose in 200 ml (37.5%), 3) 25 g glucose in 600 ml (4%), and 4) 75 g glucose in 600 ml (12.5%). GE, BP, HR, and blood glucose were measured for 180 min. After all drinks, duodenal glucose loads were similar in the first 60 min. Regardless of concentration, 600-ml (but not 200-ml) drinks initially increased BP, and in the first 30 min, systolic BP correlated (P < 0.01) with volume in both the proximal and total stomach. At the same concentration (12.5%), systolic BP fell more (P = 0.02) at the smaller volume; at the same volumes, there were no effects of concentration on BP. There was no difference in the glycemic response to drinks of identical glucose content. We conclude that 1) ingestion of glucose at a higher volume attenuates and 2) under constant duodenal load, glucose concentration (4-37%) does not affect the fall in BP.
Asunto(s)
Ingestión de Líquidos/fisiología , Vaciamiento Gástrico/fisiología , Glucosa/administración & dosificación , Hipotensión/prevención & control , Hipotensión/fisiopatología , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Glucemia/fisiología , Presión Sanguínea/fisiología , Duodeno/fisiología , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Hipotensión/etiología , Masculino , Periodo Posprandial/fisiologíaRESUMEN
The primary aims of this study were to evaluate the effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) on gastric emptying (GE) of, and the blood pressure (BP), glycemic, insulin, and incretin responses to, oral glucose in older subjects. Eight healthy subjects (4 males and 4 females, aged 70.9 +/- 1.3 yr) were studied on two separate days, in double-blind, randomized order. Subjects received an intravenous infusion of either l-NAME (180 mug.kg(-1).h(-1)) or saline (0.9%) at a rate of 3 ml/min for 150 min. Thirty minutes after the commencement of the infusion (0 min), subjects consumed a 300-ml drink containing 50 g glucose labeled with 20 MBq (99m)Tc-sulfur colloid, while sitting in front of a gamma camera. GE, BP (systolic and diastolic), heart rate (HR), blood glucose, plasma insulin, and incretin hormones, glucose-dependant insulinotropic-polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), were measured. l-NAME had no effect on GE, GIP, and GLP-1. Between -30 and 0 min l-NAME had no effect on BP or HR. After the drink (0-60 min), systolic and diastolic BP fell (P < 0.05) and HR increased (P < 0.01) during saline; these effects were attenuated (P < 0.001) by l-NAME. Blood glucose levels between 90 and 150 min were higher (P < 0.001) and plasma insulin were between 15 and 150 min less (P < 0.001) after l-NAME. The fall in BP, increase in HR, and stimulation of insulin secretion by oral glucose in older subjects were mediated by NO mechanisms by an effect unrelated to GE or changes in incretin hormones.