scholarly journals Effects of Glucagon-like Peptide-1 on the Reproductive Axis in Healthy Men

2020 ◽  
Vol 105 (4) ◽  
pp. 1119-1125 ◽  
Author(s):  
Chioma Izzi-Engbeaya ◽  
Sophie Jones ◽  
Yoshibye Crustna ◽  
Pratibha C Machenahalli ◽  
Deborah Papadopoulou ◽  
...  
Keyword(s):  
Food Intake ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Area Under The Curve ◽  
Healthy Men ◽  
Reproductive Axis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Stimulating Hormone

Abstract Context Glucagon-like peptide-1 (GLP-1) potently reduces food intake and augments glucose-stimulated insulin secretion. Recent animal data suggest that GLP-1 may also influence reproduction. As GLP-1 receptor agonists are currently widely used in clinical practice to treat obesity/type 2 diabetes, it is necessary to determine the effects of GLP-1 on the reproductive system in humans. Objective To investigate the effects of GLP-1 administration on the reproductive axis in humans. Design Single-blind, randomized, placebo-controlled crossover study. Setting Clinical Research Facility, Imperial College Healthcare NHS Trust. Participants Eighteen healthy men (mean age 24.7 ± 0.1years, mean BMI 22.1 ± 0.4kg/m2). Intervention Eight-hour intravenous infusion of 0.8 pmol/kg/min GLP-1 or rate-matched vehicle infusion. Main Outcome Measures Number of luteinizing hormone (LH) pulses, LH, follicle-stimulating hormone (FSH), and testosterone levels. Results The number of LH pulses (number of LH pulses/500 min: vehicle 4.2 ± 0.4, GLP-1 4.5 ± 0.3, P = 0.46), LH area under the curve (AUC) (vehicle 1518 ± 88min.IU/L, GLP-1 1524 ± 101min.IU/L, P = 0.95), follicle-stimulating hormone AUC (vehicle 1210 ± 112 min IU/L, GLP-1 1216 ± 112 min IU/L, P = 0.86), and testosterone AUC (vehicle 10893 ± 615 min nmol/L, GLP-1 11088 ± 792 min nmol/L, P = 0.77) did not significantly differ during vehicle and GLP-1 administration. Glucagon-like peptide-1 significantly reduced food intake (vehicle 15.7 ± 1.3 kcal/kg, GLP-1 13.4 ± 1.3 kcal/kg, P = 0.01). Conclusions In contrast to the animal literature, our data demonstrate that acute GLP-1 administration does not affect reproductive hormone secretion in healthy men.

scholarly journals Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

2016 ◽  
Vol 310 (1) ◽  
pp. G43-G51 ◽  
Author(s):  
Simon Veedfald ◽  
Astrid Plamboeck ◽  
Carolyn F. Deacon ◽  
Bolette Hartmann ◽  
Filip K. Knop ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Sham Feeding ◽  
C Peptide ◽  
Healthy Men ◽  
Glucose Levels ◽  
Gut Hormone ◽  
Cephalic Phase ◽  
Hormone Responses ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m2; HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka “chew and spit”) with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg−1·min−1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were −10.7 ± 1.1 vs. −4.0 ± 1.1 and −4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

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.

scholarly journals Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men

2014 ◽  
Vol 100 (2) ◽  
pp. 514-523 ◽  
Author(s):  
Robert E Steinert ◽  
Joerg Schirra ◽  
Anne C Meyer-Gerspach ◽  
Philipp Kienle ◽  
Heiko Fischer ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonism ◽  
Healthy Men ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake

2011 ◽  
Vol 301 (6) ◽  
pp. R1755-R1764 ◽  
Author(s):  
Naomi J. McKay ◽  
Scott E. Kanoski ◽  
Matthew R. Hayes ◽  
Derek Daniels
Keyword(s):  
Food Intake ◽  
Water Intake ◽  
Intraperitoneal Administration ◽  
Time Frame ◽  
Receptor Agonists ◽  
Mediated Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Long Acting

Glucagon-like peptide-1 (GLP-1) is produced by and released from the small intestine following ingestion of nutrients. GLP-1 receptor (GLP-1R) agonists applied peripherally or centrally decrease food intake and increase glucose-stimulated insulin secretion. These effects make the GLP-1 system an attractive target for the treatment of type 2 diabetes mellitus and obesity. In addition to these more frequently studied effects of GLP-1R stimulation, previous reports indicate that GLP-1R agonists suppress water intake. The present experiments were designed to provide greater temporal resolution and site specificity for the effect of GLP-1 and the long-acting GLP-1R agonists, exendin-4 and liraglutide, on unstimulated water intake when food was and was not available. All three GLP-1R ligands suppressed water intake after peripheral intraperitoneal administration, both in the presence of and the absence of food; however, the magnitude and time frame of water intake suppression varied by drug. GLP-1 had an immediate, but transient, hypodipsic effect when administered peripherally, whereas the water intake suppression by IP exendin-4 and liraglutide was much more persistent. Additionally, intracerebroventricular administration of GLP-1R agonists suppressed water intake when food was absent, but the suppression of intake showed modest differences depending on whether the drug was administered to the lateral or fourth ventricle. To the best of our knowledge, this is the first demonstration of GLP-1 receptor agonists affecting unstimulated, overnight intake in the absence of food, the first test for antidipsogenic effects of hindbrain application of GLP-1 receptor agonists, and the first test of a central effect (forebrain or hindbrain) of liraglutide on water intake. Overall, these results show that GLP-1R agonists have a hypodipsic effect that is independent of GLP-1R-mediated effects on food intake, and this occurs, in part, through central nervous system GLP-1R activation.

High-fat diet effects on gut motility, hormone, and appetite responses to duodenal lipid in healthy men

2003 ◽  
Vol 284 (2) ◽  
pp. G188-G196 ◽  
Author(s):  
K. A. Boyd ◽  
D. G. O'Donovan ◽  
S. Doran ◽  
J. Wishart ◽  
I. M. Chapman ◽  
...  
Keyword(s):  
Food Intake ◽  
High Fat Diet ◽  
Crossover Fashion ◽  
Plasma Glucagon ◽  
Acute Effects ◽  
High Fat ◽  
Lipid Infusion ◽  
Healthy Men ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

There is evidence that gastrointestinal function adapts in response to a high-fat (HF) diet. This study investigated the hypothesis that an HF diet modifies the acute effects of duodenal lipid on appetite, antropyloroduodenal pressures, plasma CCK and plasma glucagon-like peptide-1 (GLP-1) levels in humans. Twelve healthy men were studied twice in randomized, crossover fashion. The effects of a 90-min duodenal lipid infusion (6.3 kJ/min) on the above parameters were assessed immediately following 14-day periods on either an HF or a low-fat (LF) diet. After the HF diet, pyloric tonic and phasic pressures were attenuated, and the number of antropyloroduodenal pressure-wave sequences was increased when compared with the LF diet. Plasma CCK and GLP-1 levels did not differ between the two diets. Hunger was greater during the lipid infusion following the HF diet, but there was no difference in food intake. Therefore, exposure to an HF diet for 14 days attenuates the effects of duodenal lipid on antropyloroduodenal pressures and hunger without affecting food intake or plasma hormone levels.

scholarly journals Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1134
Author(s):  
Hao-Qi Wang ◽  
Wei-Di Zhang ◽  
Bao Yuan ◽  
Jia-Bao Zhang
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Β Subunit ◽  
Glycoprotein Hormone ◽  
Livestock Breeding ◽  
Biological Specificity ◽  
Therapeutic Development ◽  
Stimulating Hormone

Mammalian reproduction is mainly driven and regulated by the hypothalamic-pituitary-gonadal (HPG) axis. Follicle-stimulating hormone (FSH), which is synthesized and secreted by the anterior pituitary gland, is a key regulator that ultimately affects animal fertility. As a dimeric glycoprotein hormone, the biological specificity of FSH is mainly determined by the β subunit. As research techniques are being continuously innovated, studies are exploring the underlying molecular mechanism regulating the secretion of mammalian FSH. This article will review the current knowledge on the molecular mechanisms and signaling pathways systematically regulating FSH synthesis and will present the latest hypothesis about the nuclear cross-talk among the various endocrine-induced pathways for transcriptional regulation of the FSH β subunit. This article will provide novel ideas and potential targets for the improved use of FSH in livestock breeding and therapeutic development.

Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose

2013 ◽  
Vol 304 (7) ◽  
pp. E677-E685 ◽  
Author(s):  
Melissa A. Burmeister ◽  
Jennifer Ayala ◽  
Daniel J. Drucker ◽  
Julio E. Ayala
Keyword(s):  
Food Intake ◽  
Glucose Metabolism ◽  
Dependent Manner ◽  
Anorectic Effect ◽  
Dependent Inhibition ◽  
Glycolytic Inhibitor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Amp Activated Protein Kinase ◽  
Mediated Reduction

Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R). Central AMP-activated protein kinase (AMPK) is a nutrient-sensitive regulator of food intake that is inhibited by anorectic signals. The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR. This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK. The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK. Supporting previous findings, AICAR attenuated the anorectic effect elicited by intracerebroventricular (icv) administration of the GLP-1R agonist exendin-4 (Ex-4). We demonstrate that Ex-4 stimulates glycolysis and suppresses AMPK phosphorylation in a glucose-dependent manner in hypothalamic GT1-7 cells. This suggests that inhibition of AMPK and food intake by Ex-4 requires central glucose metabolism. Supporting this, the glycolytic inhibitor 2-deoxyglucose (2-DG) attenuated the anorectic effect of Ex-4. However, icv glucose did not enhance the suppression of food intake by Ex-4. AICAR had no effect on Ex-4-mediated reduction in locomotor activity. We also tested whether other carbohydrates affect the anorectic response to Ex-4. Intracerebroventricular pretreatment with the sucrose metabolite fructose, an AMPK activator, attenuated the anorectic effect of Ex-4. This potentially explains the increased food intake observed in sucrose-fed mice. In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK. We also suggest that fructose stimulates food intake by impairing central GLP-1R action. This has significant implications given the correlation between sugar consumption and obesity.

A role for inhibin in the control of follicle-stimulating hormone secretion in male rats

Life Sciences ◽  
1985 ◽  
Vol 36 (9) ◽  
pp. 889-899 ◽  
Author(s):  
Henry M. Jones ◽  
Constance L. Wood ◽  
Michael E. Rush
Keyword(s):  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Male Rats ◽  
Stimulating Hormone

scholarly journals Hindbrain glucagon-like peptide-1 neurons track intake volume and contribute to injection stress-induced hypophagia in meal-entrained rats

2016 ◽  
Vol 310 (10) ◽  
pp. R906-R916 ◽  
Author(s):  
Alison D. Kreisler ◽  
Linda Rinaman
Keyword(s):  
Food Intake ◽  
Potential Role ◽  
Liquid Diet ◽  
Neural Activation ◽  
Intracerebroventricular Injection ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Diet Intake ◽  
Published Research ◽  
Diet Type

Published research supports a role for central glucagon-like peptide 1 (GLP-1) signaling in suppressing food intake in rodent species. However, it is unclear whether GLP-1 neurons track food intake and contribute to satiety, and/or whether GLP-1 signaling contributes to stress-induced hypophagia. To examine whether GLP-1 neurons track intake volume, rats were trained to consume liquid diet (LD) for 1 h daily until baseline intake stabilized. On test day, schedule-fed rats consumed unrestricted or limited volumes of LD or unrestricted volumes of diluted (calorically matched to LD) or undiluted Ensure. Rats were perfused after the test meal, and brains processed for immunolocalization of cFos and GLP-1. The large majority of GLP-1 neurons expressed cFos in rats that consumed satiating volumes, regardless of diet type, with GLP-1 activation proportional to intake volume. Since GLP-1 signaling may limit intake only when such large proportions of GLP-1 neurons are activated, a second experiment examined the effect of central GLP-1 receptor (R) antagonism on 2 h intake in schedule-fed rats. Compared with baseline, intracerebroventricular vehicle (saline) suppressed Ensure intake by ∼11%. Conversely, intracerebroventricular injection of vehicle containing GLP-1R antagonist increased intake by ∼14% compared with baseline, partly due to larger second meals. We conclude that GLP-1 neural activation effectively tracks liquid diet intake, that intracerebroventricular injection suppresses intake, and that central GLP-1 signaling contributes to this hypophagic effect. GLP-1 signaling also may contribute to satiety after large volumes have been consumed, but this potential role is difficult to separate from a role in the hypophagic response to intracerebroventricular injection.

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