scholarly journals Peptide production and secretion in GLUTag, NCI-H716, and STC-1 cells: a comparison to native L-cells

2016 ◽  
Vol 56 (3) ◽  
pp. 201-211 ◽  
Author(s):  
Rune Ehrenreich Kuhre ◽  
Nicolai Jacob Wewer Albrechtsen ◽  
Carolyn Fiona Deacon ◽  
Emilie Balk-Møller ◽  
Jens Frederik Rehfeld ◽  
...  
Keyword(s):  
Cell Lines ◽  
Peptide Yy ◽  
Prohormone Convertase ◽  
Basal Secretion ◽  
Human Gut ◽  
Hormone Production ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Peptide Secretion

AbstractGLUTag, NCI-H716, and STC-1 are cell lines that are widely used to study mechanisms underlying secretion of glucagon-like peptide-1 (GLP-1), but the extent to which they resemble native L-cells is unknown. We used validated immunoassays for 14 different hormones to analyze peptide content (lysis samples;n= 9 from different passage numbers) or peptide secretion in response to buffer (baseline), and after stimulation with 50 mM KCl or 10 mM glucose + 10 µM forskolin/3-isobutyl-1-methylxanthine (n= 6 also different passage numbers). All cell lines produced and processed proglucagon into GLP-1, GLP-2, glicentin, and oxyntomodulin in a pattern (prohormone convertase (PC)1/3 dependent) similar to that described for human gut. All three cell lines showed basal secretion of GLP-1 and GLP-2, which increased after stimulation. In contrast to freshly isolated murine L-cells, all cell lines also expressed PC2 and secreted large amounts of pancreatic glucagon. Neurotensin and somatostatin storage was low and secretion was not consistently increased by stimulation. STC-1 cells released more glucose-dependent insulinotropic polypeptide than GLP-1 at baseline (P< 0.01) and KCl elevated its secretion (P< 0.05). Peptide YY, which normally co-localizes with GLP-1 in distal L-cells, was not detected in any of the cell lines. GLUTag and STC-1 cells also expressed vasoactive intestinal peptide, but none expressed pancreatic polypeptide or insulin. GLUTag contained and secreted large amounts of CCK, while NCI-H716 did not store this peptide and STC-1 contained low amounts. Our results show that hormone production in cell line models of the L-cell has limited similarity to the natural L-cells.

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.

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 Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides

2011 ◽  
Vol 105 (9) ◽  
pp. 1320-1328 ◽  
Author(s):  
Robert E. Steinert ◽  
Florian Frey ◽  
Antonia Töpfer ◽  
Jürgen Drewe ◽  
Christoph Beglinger
Keyword(s):  
Artificial Sweeteners ◽  
Hormone Release ◽  
Human Gut ◽  
Double Blind ◽  
Gut Hormone ◽  
Structural Analogy ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Peptide Secretion

In vitro,both carbohydrate sugars and artificial sweeteners (AS) stimulate the secretion of glucagon-like peptide-1 (GLP-1). It has been suggested that the gut tastes sugars and AS through the same mechanisms as the tongue, with potential effects on gut hormone release. We investigated whether the human gut responds in the same way to AS and carbohydrate sugars, which are perceived by lingual taste as equisweet. We focused on the secretion of gastrointestinal (GI) satiety peptides in relation to appetite perception. We performed a placebo-controlled, double-blind, six-way, cross-over trial including twelve healthy subjects. On separate days, each subject received an intragastric infusion of glucose, fructose or an AS (aspartame, acesulfame K and sucralose) dissolved in 250 ml of water or water only (control). In a second part, four subjects received an intragastric infusion of the non-sweet, non-metabolisable sugar analogue 2-deoxy-d-glucose. Glucose stimulated GLP-1 (P = 0·002) and peptide tyrosine tyrosine (PYY;P = 0·046) secretion and reduced fasting plasma ghrelin (P = 0·046), whereas fructose was less effective. Both carbohydrate sugars increased satiety and fullness (albeit not significantly) compared with water. In contrast, equisweet loads of AS did not affect gastrointestinal peptide secretion with minimal effects on appetite. 2-Deoxy-d-glucose increased hunger ratings, however, with no effects on GLP-1, PYY or ghrelin. Our data demonstrate that the secretion of GLP-1, PYY and ghrelin depends on more than the detection of (1) sweetness or (2) the structural analogy to glucose.

Colonic lactulose fermentation has no impact on glucagon-like peptide-1 and peptide-YY secretion in healthy young men

2021 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Simon Veedfald ◽  
Bolette Hartmann ◽  
Astrid Marie Gauguin ◽  
Søren Møller ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Young Men ◽  
Cell Secretion ◽  
L Cell ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Many ◽  
Peptide Secretion ◽  
The Impact

Abstract Context The colon houses most of our gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products. Objective To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state. Research Design and Methods Ten healthy young men were studied on three occasions after an overnight fast. On two study days, lactulose (20 g) was given orally, and compared to water intake on a third study day. For one of the lactulose visits participants underwent a full colonic evacuation. Over a six-hour study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen (H2), while gut peptide secretion, paracetamol and short chain fatty acid levels were measured in plasma. Results Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (p=0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting, and that fermentation and peptide secretion are not acutely related. Conclusion Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.

Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic α- and intestinal L-cell lines

2009 ◽  
Vol 296 (1) ◽  
pp. E174-E181 ◽  
Author(s):  
Diana Islam ◽  
Nina Zhang ◽  
Peixiang Wang ◽  
Hang Li ◽  
Patricia L. Brubaker ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Hormone Secretion ◽  
Peptide Hormone ◽  
Dominant Negative ◽  
Signaling Cascades ◽  
Hormone Production ◽  
L Cell ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Both Epac and PKA are effectors of the second messenger cAMP. Utilizing an exchange protein directly activated by cAMP (Epac) pathway-specific cAMP analog (ESCA), we previously reported that Epac signaling regulates proglucagon gene (gcg) expression in the glucagon-like peptide-1 (GLP-1)-producing intestinal endocrine L-cell lines GLUTag and STC-1. We now show that Epac-2 is also expressed in glucagon-producing pancreatic α-cell lines, including PKA-deficient InR1-G9 cells, and that ESCA stimulates gcg promoter and mRNA expression in the InR1-G9 cells. Using a dominant-negative Epac-2 expression plasmid (Epac-2DN), we found that Epac inhibition attenuated forskolin-stimulated gcg promoter expression in the PKA-active STC-1 cell line and blocked forskolin-stimulated gcg promoter expression in the InR1-G9 cells. Consistently, ESCA was shown to stimulate glucagon and GLP-1 production in the InR1-G9 and GLUTag cell lines, respectively. Surprisingly, ESCA treatment did not show a notable stimulation of glucagon or GLP-1 secretion from these two cell lines. This is in contrast to its ability to stimulate insulin secretion from the pancreatic INS-1 β-cell line. Our findings suggest that Epac is selectively involved in peptide hormone secretion in pancreatic and intestinal endocrine cells and that distinct signaling cascades are involved in stimulating production vs. secretion of glucagon and GLP-1 in response to cAMP elevation.

scholarly journals Changes in the Homeostatic Appetite System After Weight Loss Reflect a Normalization Toward a Lower Body Weight

2020 ◽  
Vol 105 (7) ◽  
pp. e2538-e2546 ◽  
Author(s):  
Julia Nicole DeBenedictis ◽  
Siren Nymo ◽  
Karoline Haagensli Ollestad ◽  
Guro Akersveen Boyesen ◽  
Jens Frederik Rehfeld ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Peptide Yy ◽  
Negative Impact ◽  
Control Group ◽  
Lower Body ◽  
Lower Body Weight ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Peptide Secretion

Abstract Objective To compare appetite markers in reduced-obese individuals with a nonobese control group. Methods A total of 34 adults with obesity who lost 17% body weight at week 13 and maintained this weight loss (WL) at 1 year were compared with 33 nonobese controls matched for body composition. Basal and postprandial subjective appetite ratings and appetite-related hormone concentrations (ghrelin, total peptide YY, peptide YY3-36, total and active glucagon-like peptide 1, and cholecystokinin) were measured in all participants and repeated at week 13 and 1 year in the weight-reduced group. Results WL led to a reduction in prospective food consumption and an increase in feelings of hunger, fullness, and ghrelin secretion (basal and postprandial), but these new ratings were no different from those seen in controls. Postprandial concentrations of active glucagon-like peptide 1, total peptide YY, and cholecystokinin were lower in individuals with obesity at all time points compared with controls. Conclusion The increased drive to eat (both subjective feelings of hunger and ghrelin concentrations) seen in reduced-obese individuals, both after acute and sustained WL, reflects a normalization toward a lower body weight. Overall, WL does not have a sustained negative impact on satiety peptide secretion, despite a blunted secretion in individuals with obesity compared with nonobese controls.

scholarly journals Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells

Diabetologia ◽  
2013 ◽  
Vol 56 (6) ◽  
pp. 1413-1416 ◽  
Author(s):  
A. M. Habib ◽  
P. Richards ◽  
G. J. Rogers ◽  
F. Reimann ◽  
F. M. Gribble
Keyword(s):  
Peptide Yy ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals The Melanocortin-4 Receptor Is Expressed in Enteroendocrine L Cells and Regulates the Release of Peptide YY and Glucagon-like Peptide 1 In Vivo

2014 ◽  
Vol 20 (6) ◽  
pp. 1018-1029 ◽  
Author(s):  
Brandon L. Panaro ◽  
Iain R. Tough ◽  
Maja S. Engelstoft ◽  
Robert T. Matthews ◽  
Gregory J. Digby ◽  
...  
Keyword(s):  
Peptide Yy ◽  
L Cells ◽  
Melanocortin 4 Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway

2000 ◽  
Vol 279 (5) ◽  
pp. G925-G930 ◽  
Author(s):  
G. Cuche ◽  
J. C. Cuber ◽  
C. H. Malbert
Keyword(s):  
Gastric Motility ◽  
Short Chain Fatty Acid ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Maximal Amplitude ◽  
Inhibiting Factor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 ± 1.2 vs. 49 ± 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 ± 0.11 vs. 1.3 ± 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 ± 1.0 and 34 ± 0.8 vs. 47 ± 1.3 and 43 ± 1.2%; frequency, 1.4 ± 0.07 and 1.6 ± 0.06 vs. 1.1 ± 0.14 and 1.0 ± 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

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