scholarly journals Activation of Prostaglandin E Receptor 4 Triggers Secretion of Gut Hormone Peptides GLP-1, GLP-2, and PYY

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Tamer Coskun ◽  
Libbey S. O’Farrell ◽  
Samreen K. Syed ◽  
Daniel A. Briere ◽  
Lisa S. Beavers ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Hormone Secretion ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Inhibitory Peptide ◽  
Ep Receptors ◽  
L Cells ◽  
Ep4 Receptor ◽  
Gut Hormone ◽  
Glucagon Like Peptide

Prostaglandins E1 and E2 are synthesized in the intestine and mediate a range of gastrointestinal functions via activation of the prostanoid E type (EP) family of receptors. We examined the potential role of EP receptors in the regulation of gut hormone secretion from L cells. Analysis of mRNA expression in mouse enteroendocrine GLUTag cells demonstrated the abundant expression of EP4 receptor, whereas expression of other EP receptors was much lower. Prostaglandin E1 and E2, nonselective agonists for all EP receptor subtypes, triggered glucagon like peptide 1 (GLP-1) secretion from GLUTag cells, as did the EP4-selective agonists CAY10580 and TCS2510. The effect of EP4 agonists on GLP-1 secretion was blocked by incubation of cells with the EP4-selective antagonist L161,982 or by down-regulating EP4 expression with specific small interfering RNA. Regulation of gut hormone secretion with EP4 agonists was further studied in mice. Administration of EP4 agonists to mice produced a significant elevation of plasma levels of GLP-1, glucagon like peptide 2 (GLP-2) and peptide YY (PYY), whereas gastric inhibitory peptide (GIP) levels were not increased. Thus, our data demonstrate that activation of the EP4 receptor in enteroendocrine L cells triggers secretion of gut hormones.

scholarly journals Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

2019 ◽  
Vol 316 (5) ◽  
pp. G574-G584 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Samuel Addison Jack Trammell ◽  
Nicolai Jacob Wewer Albrechtsen ◽  
Kristina Schoonjans ◽  
Reidar Albrechtsen ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Peptide Yy ◽  
Whole Body ◽  
Rat Colon ◽  
G Protein Coupled Receptor ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion.NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.

scholarly journals Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein–Coupled Bile Acid Receptors

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 3961-3970 ◽  
Author(s):  
Cheryl A. Brighton ◽  
Juraj Rievaj ◽  
Rune E. Kuhre ◽  
Leslie L. Glass ◽  
Kristina Schoonjans ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
G Protein ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Intracellular Camp ◽  
Ussing Chambers ◽  
L Cells ◽  
Gut Hormone ◽  
G Protein Coupled

Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms.

Gastrointestinal Satiety Signals III. Glucagon-like peptide 1, oxyntomodulin, peptide YY, and pancreatic polypeptide

2004 ◽  
Vol 286 (5) ◽  
pp. G693-G697 ◽  
Author(s):  
Sarah Stanley ◽  
Katie Wynne ◽  
Steve Bloom
Keyword(s):  
Gastrointestinal Tract ◽  
Animal Models ◽  
Eating Behavior ◽  
Pancreatic Polypeptide ◽  
Peptide Yy ◽  
Gastrointestinal Function ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Many peptides are synthesized and released from the gastrointestinal tract and pancreas, including pancreatic polypeptide (PP) and the products of the gastrointestinal L cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY). Whereas their roles in regulation of gastrointestinal function have been known for some time, it is now evident that they also influence eating behavior. This review considers the anorectic peptides PYY, PP, GLP-1, and oxyntomodulin, which decrease appetite and promote satiety in both animal models and humans.

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 The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 585 ◽  
Author(s):  
Brandon Boland ◽  
Michael Mumphrey ◽  
Zheng Hao ◽  
Benji Gill ◽  
R. Townsend ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Body Composition ◽  
Body Weight ◽  
High Fat Diet ◽  
Peptide Yy ◽  
Body Weight Loss ◽  
Receptor Subtypes ◽  
High Fat ◽  
Knockout Mouse Model ◽  
Gut Hormone

Background/Goals: The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.

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 &lt; 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 &lt; 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 Hypoglycemic effect and mechanism of isoquercitrin as an inhibitor of dipeptidyl peptidase-4 in type 2 diabetic mice

RSC Advances ◽  
2018 ◽  
Vol 8 (27) ◽  
pp. 14967-14974 ◽  
Author(s):  
Lei Zhang ◽  
Shi-Tao Zhang ◽  
Yan-Chun Yin ◽  
Shu Xing ◽  
Wan-Nan Li ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Hypoglycemic Effect ◽  
Diabetic Mice ◽  
Dipeptidyl Peptidase 4 ◽  
L Cells ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Type 2 Diabetic

Glucagon-like peptide (GLP)-1 is a potent glucose-dependent insulinotropic gut hormone released from intestinal L cells.

Differential localization of prostaglandin E receptor subtypes in human kidney

1996 ◽  
Vol 270 (5) ◽  
pp. F912-F918 ◽  
Author(s):  
M. D. Breyer ◽  
L. Davis ◽  
H. R. Jacobson ◽  
R. M. Breyer
Keyword(s):  
In Situ Hybridization ◽  
Collecting Duct ◽  
Human Kidney ◽  
Prostaglandin E ◽  
Receptor Subtypes ◽  
Ep Receptors ◽  
Inner Medullary Collecting Duct ◽  
Ep Receptor ◽  
Medullary Collecting Duct

Four prostaglandin E2 (PGE2) receptors designated EP1, EP2, EP3, and EP4 have been pharmacologically identified, cloned, and sequenced. The present studies determined the intrarenal distribution of these EP-receptor subtypes in human kidney using in situ hybridization with riboprobes for the human EP receptors. mRNA for the phosphatidylinositol hydrolysis-coupled EP receptor was highly expressed in cortical, outer medullary, and inner medullary collecting duct. RNA for the Gi-coupled EP3 receptor was primarily expressed in the cortical and outer medullary collecting duct, as well as in the medullary thick ascending limb; however, it was absent from the inner medullary collecting duct. Expression of mRNA for EP1 and EP3 in connecting segment could not be excluded. There was no expression of the GS-coupled EP2 receptor mRNA detected in human kidney by in situ hybridization; however, mRNA for the GS-coupled EP4 receptor was highly expressed in the glomerulus. These studies demonstrate distinct regions of intrarenal expression for the different EP receptors and suggest that each receptor subtype may modulate different aspects of renal function in humans.

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.

scholarly journals Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

2010 ◽  
Vol 162 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Solrun Vidarsdottir ◽  
Ferdinand Roelfsema ◽  
Trea Streefland ◽  
Jens J Holst ◽  
Jens F Rehfeld ◽  
...  
Keyword(s):  
Weight Gain ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Healthy Men ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1

BackgroundTreatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth, might cause less weight gain than olanzapine standard oral tablets (OST).Design and methodsTen healthy men received olanzapine ODT (10 mg o.d., 8 days), olanzapine OST (10 mg o.d., 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, blood samples were taken for measurement of pancreatic polypeptide, peptide YY, glucagon-like peptide-1, total glucagon, total ghrelin, and cholecystokinin (CCK) concentrations.ResultsWith the exception of pre- and postprandial concentration of ghrelin at dinner and preprandial CCK concentrations at breakfast, which were all slightly increased (respectivelyP=0.048,P=0.034 andP=0.042), olanzapine did not affect gut hormone concentrations. Thus, olanzapine ODT and OST had similar effects on gut hormone secretion.ConclusionShort-term treatment with olanzapine does not have major impact on the plasma concentration of gut hormones we measured in healthy men. Moreover, despite pharmacological difference, gut hormone concentrations are similar during treatment with olanzapine ODT and OST. The capacity of olanzapine to induce weight gain and diabetes is unlikely to be caused by modulation of the secretion of gut hormones measured here. We cannot exclude the possibility that olanzapine's impact on other gut hormones, to impair insulin sensitivity and stimulate weight gain, exists.

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