scholarly journals Ghrelin Stimulates Gastric Emptying and Hunger in Normal-Weight Humans

2006 ◽  
Vol 91 (9) ◽  
pp. 3296-3302 ◽  
Author(s):  
F. Levin ◽  
T. Edholm ◽  
P. T. Schmidt ◽  
P. Grybäck ◽  
H. Jacobsson ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Normal Weight ◽  
Lag Phase ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
Ghrelin Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. Main Objective: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. Design: This was a randomized, double-blind, crossover study. Subjects: Subjects included normal human volunteers and patients with GH deficiency. Intervention: Intervention included saline or ghrelin (10 pmol/kg·min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. Main Outcome Measures: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. Results: The emptying rate was significantly faster for ghrelin (1.26 ± 0.1% per minute), compared with saline (0.83% per minute) (P < 0.001). The lag phase (16.2 ± 2.2 and 26.5 ± 3.8 min) and half-emptying time (49.4 ± 3.9 and 75.6 ± 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P < 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. Conclusion: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.

scholarly journals Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

2004 ◽  
Vol 91 (3) ◽  
pp. 439-446 ◽  
Author(s):  
Erik Näslund ◽  
N. King ◽  
S. Mansten ◽  
N. Adner ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Emptying ◽  
Food Intake ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
Subcutaneous Injections ◽  
Subcutaneous Infusion ◽  
Continuous Subcutaneous Infusion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Recombinant glucagon-like peptide-1 (7–36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5d by prandial subcutaneous injections (PSI) (76nmol 30min before meals, four times daily; a total of 302·4nmol/24h) or by continuous subcutaneous infusion (CSI) (12·7nmol/h; a total of 304·8nmol/24h). This was performed in nineteen healthy obese subjects (mean age 44·2 (sem 2·5) years; BMI 39·0 (sem 1·2)kg/m2) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15% reduction in mean food intake per meal (P=0·02) after 5d treatment. A weight loss of 0·55 (sem 0·2) kg (P<0·05) was registered after 5d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0·001) and CSI (P<0·05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.

Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

2001 ◽  
Vol 281 (3) ◽  
pp. G752-G763 ◽  
Author(s):  
Feruze Y. Enç ◽  
Neşe I˙meryüz ◽  
Levent Akin ◽  
Turgut Turoğlu ◽  
Fuat Dede ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Peptide Yy ◽  
Area Under The Curve ◽  
Gut Hormones ◽  
Random Order ◽  
Mixed Meal ◽  
Carbohydrate Absorption ◽  
Plasma Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

We investigated the effect of acarbose, an α-glucosidase and pancreatic α-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 ( r = 0.68 , P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.

scholarly journals Effects of oligofructose on appetite profile, glucagon-like peptide 1 and peptide YY3-36 concentrations and energy intake

2011 ◽  
Vol 106 (11) ◽  
pp. 1757-1762 ◽  
Author(s):  
Sanne P. M. Verhoef ◽  
Diederick Meyer ◽  
Klaas R. Westerterp
Keyword(s):  
Energy Intake ◽  
Human Subjects ◽  
Hormone Secretion ◽  
Area Under The Curve ◽  
Double Blind ◽  
Time Treatment ◽  
Satiety Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Reduce Energy Intake

In rats, oligofructose has been shown to stimulate satiety hormone secretion, reduce energy intake and promote weight loss. The present study aimed to examine the effect of oligofructose supplementation on appetite profiles, satiety hormone concentrations and energy intake in human subjects. A total of thirty-one healthy subjects (ten men and twenty-one women) aged 28 (sem 3) years with a BMI of 24·8 (sem 0·3) kg/m2 were included in a randomised double-blind, cross-over study. The subjects received 10 g oligofructose, 16 g oligofructose or 16 g placebo (maltodextrin) daily for 13 d, with a 2-week washout period between treatments. Appetite profile, active glucagon-like peptide 1 (GLP-1) and peptide YY3-36 (PYY) concentrations and energy intake were assessed on days 0 and 13 of the treatment period. Time × treatment interaction revealed a trend of reduction in energy intake over days 0–13 by oligofructose (P = 0·068). Energy intake was significantly reduced (11 %) over time on day 13 compared with day 0 with 16 g/d oligofructose (2801 (sem 301) v. 3217 (sem 320) kJ, P < 0·05). Moreover, energy intake was significantly lower with 16 g/d oligofructose compared with 10 g/d oligofructose on day 13 (2801 (sem 301) v. 3177 (sem 276) kJ, P < 0·05). Area under the curve (AUC) for GLP-1 on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose (45 (sem 4) v. 41 (sem 3) pmol/l × h, P < 0·05). In the morning until lunch, AUC0–230 min for PYY on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose and placebo (409 (sem 35) v. 222 (sem 19) and 211 (sem 20) pg/ml × h, P < 0·01). In conclusion, 16 g/d and not 10 g/d oligofructose may be an effective dose to reduce energy intake, possibly supported by higher GLP-1 and PYY concentrations.

Mechanisms of gastric emptying disturbances in chronic and acute inflammation of the distal gastrointestinal tract

2009 ◽  
Vol 297 (5) ◽  
pp. G861-G868 ◽  
Author(s):  
Jutta Keller ◽  
Christoph Beglinger ◽  
Jens Juul Holst ◽  
Viola Andresen ◽  
Peter Layer
Keyword(s):  
Gastrointestinal Tract ◽  
Gastric Emptying ◽  
Plasma Glucose ◽  
Peptide Yy ◽  
Postprandial Plasma Glucose ◽  
Patient Groups ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Upper Gastrointestinal ◽  
Cck Release

It is unclear why patients with inflammation of the distal bowel complain of symptoms referable to the upper gastrointestinal tract, specifically to gastric emptying (GE) disturbances. Thus we aimed to determine occurrence and putative pathomechanisms of gastric motor disorders in such patients. Thirteen healthy subjects (CON), 13 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 7 with diverticulitis (DIV) underwent a standardized 13C-octanoic acid gastric emptying breath test. Plasma glucose, CCK, peptide YY, and glucagon-like peptide-1 (GLP-1) were measured periodically and correlated with GE parameters. Results were given in means ± SD. Compared with CON, GE half time (T) was prolonged by 50% in CD (115 ± 55 vs. 182 ± 95 min, P = 0.037). Six CD, 2 DIV, and 2 UC patients had pathological T (>200 min). Postprandial plasma glucose was increased in all patients but was highest in DIV and correlated with T ( r = 0.90, P = 0.006). In CD, mean postprandial CCK levels were increased threefold compared with CON (6.5 ± 6.7 vs. 2.1 ± 0.6 pmol/l, P = 0.027) and were correlated with T ( r = 0.60, P = 0.041). Compared with CON, GLP-1 levels were increased in UC (25.1 ± 5.2 vs. 33.5 ± 13.0 pmol/l, P = 0.046) but markedly decreased in DIV (9.6 ± 5.2 pmol/l, P < 0.0001). We concluded that a subset of patients with CD, UC, or DIV has delayed GE. GE disturbances are most pronounced in CD and might partly be caused by excessive CCK release. In DIV there might be a pathophysiological link between decreased GLP-1 release, postprandial hyperglycemia, and delayed GE. These explorative data encourage further studies in larger patient groups.

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

2007 ◽  
Vol 293 (6) ◽  
pp. R2170-R2178 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Penny Papadopoulos ◽  
Ixchel M. Brennan ◽  
Tanya J. Little ◽  
James H. Meyer ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Energy Intake ◽  
Peptide Yy ◽  
Saline Control ◽  
Double Blind ◽  
Gastric Emptying Rate ◽  
The Mean ◽  
Small Intestinal ◽  
Healthy Males ◽  
Cck Release

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.

scholarly journals Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1

2019 ◽  
Vol 105 (1) ◽  
pp. 266-275 ◽  
Author(s):  
Sara Lind Jepsen ◽  
Esben Thyssen Vestergaard ◽  
Pierre Larraufie ◽  
Fiona Mary Gribble ◽  
Frank Reimann ◽  
...  
Keyword(s):  
Small Intestine ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Receptor Expression ◽  
Gastrointestinal Hormone ◽  
Ghrelin Receptor ◽  
L Cells ◽  
Mouse Small Intestine ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Context The gastrointestinal hormone ghrelin stimulates growth hormone secretion and appetite, but recent studies indicate that ghrelin also stimulates the secretion of the appetite-inhibiting and insulinotropic hormone glucagon-like peptide-1 (GLP-1). Objective To investigate the putative effect of ghrelin on GLP-1 secretion in vivo and in vitro. Subjects and Methods A randomized placebo-controlled crossover study was performed in eight hypopituitary subjects. Ghrelin or saline was infused intravenously (1 pmol/min × kg) after collection of baseline sample (0 min), and blood was subsequently collected at time 30, 60, 90, and 120 minutes. Mouse small intestine was perfused (n = 6) and GLP-1 output from perfused mouse small intestine was investigated in response to vascular ghrelin administration in the presence and absence of a simultaneous luminal glucose stimulus. Ghrelin receptor expression was quantified in human (n = 11) and mouse L-cells (n = 3) by RNA sequencing and RT-qPCR, respectively. Results Ghrelin did not affect GLP-1 secretion in humans (area under the curve [AUC; 0–120 min]: ghrelin infusion = 1.37 ± 0.05 min × nmol vs. saline infusion = 1.40 ± 0.06 min × nmol [P = 0.63]), but induced peripheral insulin resistance. Likewise, ghrelin did not stimulate GLP-1 secretion from the perfused mouse small intestine model (mean outputs during baseline/ghrelin infusion = 19.3 ± 1.6/25.5 ± 2.0 fmol/min, n = 6, P = 0.16), whereas glucose-dependent insulinotropic polypeptide administration, used as a positive control, doubled GLP-1 secretion (P &lt; 0.001). Intraluminal glucose increased GLP-1 secretion by 4-fold (P &lt; 0.001), which was not potentiated by ghrelin. Finally, gene expression of the ghrelin receptor was undetectable in mouse L-cells and marginal in human L-cells. Conclusions Ghrelin does not interact directly with the L-cell and does not directly affect GLP-1 secretion.

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