Timing of Meal Ingestion Determines Gastric Emptying of a Test Drink

AbstractTo determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated Gfralcre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to the aversive suppression of nutrient uptake and absorption.

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Gastric Emptying of a Solid Meal Starts during Meal Ingestion: Combined Study Using 13C-Octanoic Acid Breath Test and Doppler Ultrasonography

Digestion ◽

10.1159/000080088 ◽

2004 ◽

Vol 70 (1) ◽

pp. 55-60 ◽

Cited By ~ 19

Author(s):

Itta M. Minderhoud ◽

Marco W. Mundt ◽

Jan M.M. Roelofs ◽

Melvin Samsom

Keyword(s):

Gastric Emptying ◽

Breath Test ◽

Doppler Ultrasonography ◽

Octanoic Acid ◽

Solid Meal ◽

Meal Ingestion

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Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation

Pharmaceutics ◽

10.3390/pharmaceutics12090790 ◽

2020 ◽

Vol 12 (9) ◽

pp. 790 ◽

Cited By ~ 1

Author(s):

Cong Xie ◽

Karen L. Jones ◽

Christopher K. Rayner ◽

Tongzhi Wu

Keyword(s):

Gastric Emptying ◽

Hormone Secretion ◽

Gastrointestinal Hormones ◽

Postprandial Glucose ◽

Gastrointestinal Hormone ◽

Postprandial Metabolism ◽

Secretion Profile ◽

Meal Ingestion ◽

Small And Large Intestine

It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from specialised enteroendocrine cells (EECs) distributed in various regions of the gut, which in turn to regulate gastric emptying, appetite and postprandial glucose metabolism. Stimulation of gastrointestinal hormone secretion, therefore, represents a promising strategy for the management of metabolic disorders, particularly obesity and type 2 diabetes mellitus (T2DM). That EECs are distributed distinctively between the proximal and distal gut suggests that the region of the gut exposed to intraluminal stimuli is of major relevance to the secretion profile of gastrointestinal hormones and associated metabolic responses. This review discusses the process of intestinal digestion and absorption and their impacts on the release of gastrointestinal hormones and the regulation of postprandial metabolism, with an emphasis on the differences between the proximal and distal gut, and implications for the management of obesity and T2DM.

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Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa854 ◽

2020 ◽

Author(s):

Tejaswini Arunachala Murthy ◽

Jacqueline Grivell ◽

Seva Hatzinikolas ◽

Lee-anne S Chapple ◽

Marianne J Chapman ◽

...

Keyword(s):

Blood Glucose ◽

Gastric Emptying ◽

Severe Hypoglycemia ◽

Random Order ◽

Solid Meal ◽

Major Barrier ◽

Postprandial Glycemia ◽

Meal Ingestion ◽

The Impact

Abstract Context Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized “non-severe” hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. “Marked” hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of “mild” hypoglycemia (3.0-3.9 mmol/L) is unknown. Objective To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L (“marked”) and 3.6 mmol/L (“mild”), on gastric emptying in health. Design, Setting, and Subjects Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. Results Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia. Conclusion In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.

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Consumption of Carbonated and Noncarbonated Sports Drinks during Prolonged Treadmill Exercise in the Heat

International Journal of Sport Nutrition ◽

10.1123/ijsn.1.3.225 ◽

1991 ◽

Vol 1 (3) ◽

pp. 225-239 ◽

Cited By ~ 11

Author(s):

Alan J. Ryan ◽

Amy E. Navarre ◽

Carl V. Gisolfi

Keyword(s):

Gastric Emptying ◽

Perceived Exertion ◽

Treadmill Exercise ◽

Sweat Rate ◽

Ratings Of Perceived Exertion ◽

Mean Values ◽

Sports Drinks ◽

Ad Libitum ◽

Test Drink ◽

Carbonated Drink

These studies were done to determine the effect of carbonation and carbohydrate content on either gastric emptying or ad libitum drinking during treadmill exercise in the heat. Four test drinks were used: a 6% carbohydrate, noncarbonated; a 6% carbohydrate, carbonated; a 10% carbohydrate, noncarbonated; and a 10% carbohydrate, carbonated drink. For gastric emptying studies, subjects completed four 1-hr treadmill runs in the heat. They were given 400 mL of test drink at 0 rnin and 200 mL at 15, 30, and 45 min of exercise. For ad libitum drinking studies, subjects completed four 2-hr treadmill runs in the heat. Gastric residual volumes were similar during the four 1-hr runs. During the 2-hr runs, ad libitum drinking of the four beverages was also similar. Mean values for sweat rate, percentage of body weight lost, and percentage of fluid replaced by ad libitum drinking were similar for the four trials. Similar changes in heart rate, rectal temperature, and ratings of perceived exertion were also observed during the four 2-hr treadmill runs. We conclude that the presence of carbonation in a carbohydrate drink did not have a significant effect on either gastric emptying or ad libitum drinking.

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Using gastric emptying scintigraphy to evaluate antral contractions and duodenal bolus propagation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00274.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. G203-G209

Author(s):

Perry Orthey ◽

Simin Dadparvar ◽

Bhishak Kamat ◽

Henry P. Parkman ◽

Alan H. Maurer

Keyword(s):

Gastric Emptying ◽

Region Of Interest ◽

Sulfur Colloid ◽

Gastric Emptying Scintigraphy ◽

Gastrointestinal Dysmotility ◽

Static Images ◽

Unexplained Symptoms ◽

Meal Ingestion ◽

Dynamic Scintigraphy ◽

Upper Gastrointestinal

Our aim was to investigate the feasibility of measuring antral contractions and duodenal bolus propagation (DBP) during dynamic antral contraction scintigraphy (DACS) as an assessment of antro-pyloro-duodenal coordination (APDC). Gastric emptying scintigraphy (GES) with DACS was performed with Tc-99m sulfur colloid (SC) using increasing doses of 74 MBq (2 mCi) for 10 subjects, 185 MBq (5 mCi) for 11, and 370 MBq (10 mCi) for 11. DACS was performed for 10 min after static images at 0, 30, 60, 120, 180, and 240 min in anterior and right anterior oblique (RAO) projections. Best projection and lowest dose of Tc-99m SC were assessed visually. DBP were quantified utilizing duodenal activity peaks from a region of interest in the first portion of the duodenum. DBP was better visualized in the RAO projection than anterior projection and using 185 MBq (5 mCi) and 370 MBq (10 mCi) compared with 74 MBq (2 mCi). DBP showed infrequent and irregular bolus transfers from the antrum to the duodenum. Antral activity peaks at 60 min averaged 2.91 ± 0.66 per minute and duodenum bolus peaks 0.36 ± 0.18 per minute (ratio 0.36/2.91 = 0.12). DBP activity peaks can be measured during GES with DACS but requires a 185-MBq (5 mCi) dose of Tc-99m SC radiolabeled test meal for adequate DBP signal detection and is better imaged in RAO than anterior projection. DBPs over the first 60 min postmeal ingestion are infrequent with only 12% of the antral contractions propagating into the duodenum. This methodology appears promising to assess APDC. NEW & NOTEWORTHY This study shows that duodenal bolus propagations after meal ingestion can be measured during gastric emptying scintigraphy using dynamic scintigraphy. Duodenal bolus propagation over the first 60 min postmeal ingestion are infrequent with only 12% of the antral contractions propagating into the duodenum. This methodology appears promising to assess antropyloroduodenal coordination in patients with unexplained symptoms of upper gastrointestinal dysmotility.

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Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats

British Journal Of Nutrition ◽

10.1017/s0007114515000550 ◽

2015 ◽

Vol 113 (9) ◽

pp. 1477-1488 ◽

Cited By ~ 18

Author(s):

Shingo Nakajima ◽

Tohru Hira ◽

Hiroshi Hara

Keyword(s):

Gastric Emptying ◽

Glucose Intolerance ◽

Control Group ◽

Mrna Levels ◽

High Fat ◽

Gut Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Meal Ingestion ◽

High Sucrose

Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity.

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Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00499.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. E621-E625 ◽

Cited By ~ 79

Author(s):

Juris J. Meier ◽

Oliver Goetze ◽

Jens Anstipp ◽

Dirk Hagemann ◽

Jens J. Holst ◽

...

Keyword(s):

Gastric Emptying ◽

Repeated Measures ◽

Venous Blood ◽

Area Under The Curve ◽

Gastric Inhibitory Polypeptide ◽

Time Pattern ◽

C Peptide ◽

Gut Hormone ◽

Glucagon Like Peptide 1 ◽

Meal Ingestion

The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess “enterogastrone” activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 ± 3.3 yr, body mass index 23.7 ± 2.3 kg/m2) were studied with the intravenous infusion of GIP (2 pmol·kg-1·min-1) or placebo, each administered to the volunteers on separate occasions from -30 to 360 min in the fasting state. At 0 min, a solid test meal (250 kcal containing [13C]sodium octanoate) was served. Gastric emptying was calculated from the 13CO2 exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 ± 15 pmol/l for total and 34 ± 4 pmol/l for intact GIP ( P < 0.0001). Meal ingestion further increased GIP concentrations in both groups, reaching peak levels of 265 ± 20 and 82 ± 9 pmol/l for total and 67 ± 7 and 31 ± 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively ( P < 0.0001). There were no differences in glucose, insulin, and C-peptide between the experiments with the infusion of GIP or placebo. Gastric half-emptying times were 120 ± 9 and 120 ± 18 min ( P = 1.0, with GIP and placebo, respectively). The time pattern of gastric emptying was similar in the two groups ( P = 0.98). Endogenous GIP secretion, as derived from the incremental area under the curve of plasma GIP concentrations in the placebo experiments, did not correlate to gastric half-emptying times ( r2 = 0.15, P = 0.15 for intact GIP; r2 = 0.21, P = 0.086 for total GIP). We conclude that gastric emptying does not appear to be influenced by GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous administration. The lack of effect of GIP on gastric emptying underlines the differences between GIP and the second incretin glucagon-like peptide 1.

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Restraint stress delays solid gastric emptying via a central CRF and peripheral sympathetic neuron in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00499.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. R427-R432 ◽

Cited By ~ 89

Author(s):

Yukiomi Nakade ◽

Daisuke Tsuchida ◽

Hiroyuki Fukuda ◽

Masahiro Iwa ◽

Theodore N. Pappas ◽

...

Keyword(s):

Gastric Emptying ◽

Restraint Stress ◽

Delayed Gastric Emptying ◽

Sympathetic Neuron ◽

Inhibitory Effect ◽

Sprague Dawley ◽

Solid Meal ◽

Celiac Ganglionectomy ◽

Meal Ingestion ◽

Sympathetic Pathway

Central corticotropin-releasing factor (CRF) delays gastric emptying through the autonomic nervous system. CRF plays an important role in mediating delayed gastric emptying induced by stress. However, it is not clear whether a sympathetic or parasympathetic pathway is involved in the mechanism of central CRF-induced inhibition of solid gastric emptying. The purpose of this study was to investigate whether 1) CRF inhibits solid gastric emptying via a peripheral sympathetic pathway and 2) stress-induced inhibition of solid gastric emptying is mediated via a central CRF and peripheral sympathetic pathways. Using male Sprague-Dawley rats, CRF was injected intracisternally with or without various adrenergic-blocking agents. To investigate whether central CRF-induced inhibition of solid gastric emptying is mediated via a peripheral sympathetic pathway, rats underwent celiac ganglionectomy 1 wk before the gastric emptying study. After solid meal ingestion (90 min), gastric emptying was calculated. To investigate the role of endogenous CRF in stress-induced delayed gastric emptying, a CRF type2receptor antagonist, astressin2-B, was intracisternally administered. Rats were subjected to a restraint stress immediately after the feeding. Intracisternal injection of CRF (0.1–1.0 μg) dose-dependently inhibited solid gastric emptying. The inhibitory effect of CRF on solid gastric emptying was significantly blocked by guanethidine, propranolol, and celiac ganglionectomy but not by phentolamine. Restraint stress significantly delayed solid gastric emptying, which was improved by astressin2-B, guanethidine, and celiac ganglionectomy. Our research suggests that restraint stress inhibits solid gastric emptying via a central CRF type2receptor and peripheral sympathetic neural pathway in rats.

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