Luminal glucagon-like peptide-1(7–36) amide-releasing factors in the isolated vascularly perfused rat colon

Abstract Glucagon-like peptide-1 (GLP-1) is released from endocrine cells of the distal part of the gut after ingestion of a meal. GLP-1 secretion is, in part, under the control of hormonal and/or neural mechanisms. However, stimulation of the colonic L cells may also occur directly by the luminal contents. This was examined in the present study, using an isolated vascularly perfused rat colon. GLP-1 immunoreactivity was measured in the portal effluent after luminal infusion of a variety of compounds which are found in colonic contents (nutrients, fibers, bile acids, short-chain fatty acids (SCFAs)). Oleic acid (100 mm) or a mixture of amino acids (total concentration 250 mm), or starch (0·5%, w/v) did not increase GLP-1 secretion over basal value. A pharmacological concentration of glucose (250 mm) elicited a marked release of GLP-1 which was maximal at the end of infusion (400% of basal), while 5 mm glucose was without effect on secretion. Pectin evoked a dose-dependent release of GLP-1 over the range 0·1–0·5% (w/v) with a maximal response at 360% of basal when 0·5% pectin was infused. Cellulose or gum arabic (0·5%) did not modify GLP-1 secretion. The SCFAs acetate, propionate or butyrate (5, 20 and 100 mm) did not induce a significant release of GLP-1. Among the four bile acids tested, namely taurocholate, cholate, deoxycholate and hyodeoxycholate, the last one was the most potent at eliciting a GLP-1 response with a maximal release at 300% and 400% of the basal value when 2 and 20 mm bile acid were administered respectively. In conclusion, some fibres and bile acids are capable of releasing colonic GLP-1 in rats and may contribute to the secretory activity of colonic L cells. Journal of Endocrinology (1995) 145, 521–526

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00010.2019 ◽

2019 ◽

Vol 316 (5) ◽

pp. G574-G584 ◽

Cited By ~ 9

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.

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Luminal peptide YY-releasing factors in the isolated vascularly perfused rat colon

Journal of Endocrinology ◽

10.1677/joe.0.1510421 ◽

1996 ◽

Vol 151 (3) ◽

pp. 421-429 ◽

Cited By ~ 54

Author(s):

P Plaisancié ◽

V Dumoulin ◽

J-A Chayvialle ◽

J-C Cuber

Keyword(s):

Amino Acids ◽

Oleic Acid ◽

Peptide Yy ◽

Total Concentration ◽

Gum Arabic ◽

Rat Colon ◽

Maximal Response ◽

L Cells ◽

Releasing Factors ◽

Dose Dependent

Abstract Peptide YY (PYY) is produced in endocrine L cells primarily localized in the distal bowel. These open-type L cells make contact with the intestinal chyme which may thus affect their secretory activity. The aim of the present study was to examine a large variety of luminal compounds found in colonic contents for their potential as PYY-releasing factors, using the isolated vascularly perfused rat colon. The release of PYY into the portal effluent was measured by a specific RIA. Luminal administration of 5 mm glucose or 0·5% (w/v) starch for 30 min did not induce significant release of PYY. Oleic acid (10 and 100 mm) also did not significantly increase PYY secretion. A pharmacological concentration of glucose (250 mm) and a mixture of amino acids (total concentration 250 mm) both induced PYY secretion (200% of basal). Pectin, a polygalacturonic acid, evoked dose-dependent secretion of PYY-like immunoreactivity over the range 0·1–0·5% (w/v). The maximal response was observed after infusion of 0·5% pectin which induced a prompt and sustained release of PYY (300% of basal). Galacturonic acid itself (5%) produced marked PYY secretion. Gum arabic (0·5%) induced a gradual increase in portal PYY concentration (maximal response 250% of the basal value) whereas cellulose (0·5%) did not elicit PYY secretion. Luminal n-butyrate over the range 0·5–5 mm produced a dose-dependent release of PYY (maximal response 300% of the basal value with 5 mm n-butyrate). Increasing the concentration of n-butyrate to 100 mm provoked a gradual decrease in PYY secretion. Propionate was a less potent stimulant than n-butyrate, and acetate did not increase PYY secretion above the basal value. At a concentration of 2 or 20 mm, taurocholate, cholate and deoxycholate brought about PYY secretion while hyodeoxycholate was without effect. In conclusion, glucose and amino acids may mediate PYY release but only when they are present at high supraphysiological concentrations in the colon while oleic acid does not produce any PYY secretion. Physiological concentrations of fibers (pectin, gum arabic), short-chain fatty acids (n-butyrate, propionate) and bile salts (taurocholate, cholate, deoxycholate) are all potent stimulants of PYY release. Whether the release of PYY by luminal factors is coupled to water and electrolyte transfer via a local/paracrine pathway remains an open question which requires additional work with the isolated vascularly perfused colon preparation. Journal of Endocrinology (1996) 151, 421–429

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The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00346.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. G53-G65 ◽

Cited By ~ 66

Author(s):

Charlotte Bayer Christiansen ◽

Maria Buur Nordskov Gabe ◽

Berit Svendsen ◽

Lars Ove Dragsted ◽

Mette Marie Rosenkilde ◽

...

Keyword(s):

Energy Source ◽

Fatty Acids ◽

Fatty Acid ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Rat Colon ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Free Fatty Acid Receptors ◽

Chain Fatty Acids

The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of glucagon like peptide-1 (GLP-1)- and peptide-YY (PYY)-secreting L cells is of great interest because of the potential antidiabetic and antiobesity effects of GLP-1 and PYY. Short-chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate, and butyrate. We show that luminal and especially vascular infusion of acetate and butyrate significantly increases colonic GLP-1 secretion, and to a minor extent also PYY secretion, but only after enhancement of intracellular cAMP. Propionate neither affected GLP-1 nor PYY secretion whether administered luminally or vascularly. A FFAR2- and FFAR3–specific agonist [( S)-2-(4-chlorophenyl)-3,3-dimethyl- N-(5-phenylthiazol-2-yl)butamide (CFMB)/ AR420626 ] had no effect on colonic GLP-1 output, and a FFAR3 antagonist ( AR399519 ) did not decrease the SCFA-induced GLP-1 response. However, the voltage-gated Ca2+-channel blocker nifedipine, the KATP-channel opener diazoxide, and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses. FFAR2 receptor studies confirmed low-potent partial agonism of acetate, propionate, and butyrate, compared with CFMB, which is a full agonist with ~750-fold higher potency than the SCFAs. In conclusion, SCFAs may increase colonic GLP-1/PYY secretion, but FFAR2/FFAR3 do not seem to be involved. Rather, SCFAs are metabolized and appear to function as a colonocyte energy source.NEW & NOTEWORTHY By the use of in situ isolated perfused rat colon we show that short-chain fatty acids (SCFAs) primarily are used as a colonocyte energy source in the rat, subsequently triggering glucagon like peptide-1 (GLP-1) secretion independent of the free fatty acid receptors FFAR2 and FFAR3. Opposite many previous studies on SCFAs and FFAR2/FFAR3 and GLP-1 secretion, this experimental model allows investigation of the physiological interactions between luminal nutrients and secretion from cells whose function depend critically on their blood supply as well as nerve and paracrine interactions.

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Mechanisms underlying the prokinetic effects of endogenous glucagon-like peptide-1 in the rat proximal colon

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00175.2021 ◽

2021 ◽

Author(s):

Hiroyuki Nakamori ◽

Koji Iida ◽

Hikaru Hashitani

Keyword(s):

Fatty Acids ◽

Receptor Antagonist ◽

Short Chain Fatty Acids ◽

Proximal Colon ◽

Afferent Neurons ◽

L Cells ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Peristaltic Contractions ◽

Stimulation Of

Glucagon-like peptide-1 (GLP-1), a well-known insulin secretagogue, is released from enteroendocrine L cells both luminally and basolaterally to exert different effects. Basolaterally released GLP-1 increases epithelial ion transport by activating CGRP-containing enteric afferent neurons. Although bath-applied GLP-1 reduced the contractility of colonic segments, GLP-1-induced stimulation of afferent neurons could also accelerate peristaltic contractions. Here, the roles of endogenous GLP-1 in regulating colonic peristalsis were investigated using isolated colonic segments. Isolated segments of rat proximal colon were placed in an organ bath, serosally perfused with oxygenated physiological salt solution and luminally perfused with degassed 0.9% saline. Colonic wall motion was recorded using a video camera and converted into spatio-temporal maps. Intraluminal administration of GLP-1 (100 nM) stimulating the secretion of GLP-1 from L cells increased the frequency of oro-aboral propagating peristaltic contractions. The acceleratory effect of GLP-1 was blocked by luminally-applied exendin-3 (9-39) (100 nM), a GLP-1 receptor antagonist. GLP-1-induced acceleration of peristaltic contractions was also prevented by bath-applied BIBN4069 (1 μM), a CGRP receptor antagonist. In colonic segments that had been exposed to bath-applied capsaicin (100 nM) that desensitizes extrinsic afferents, GLP-1 was still capable of exerting its prokinetic effect. Stimulation of endogenous GLP-1 secretion with a luminally-applied cocktail of short-chain fatty acids (1 mM) increased the frequency of peristaltic waves in an exendin-3 (9-39)-sensitive manner. Thus, GLP-1 activates CGRP-expressing intrinsic afferents to accelerate peristalsis in the proximal colon. Short-chain fatty acids appear to stimulate endogenous GLP-1 secretion from L cells resulting in the acceleration of colonic peristalsis.

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Expression of cholecystokinin2-receptor in rat and human L cells and the stimulation of glucagon-like peptide-1 secretion by gastrin treatment

Acta Histochemica ◽

10.1016/j.acthis.2014.12.007 ◽

2015 ◽

Vol 117 (2) ◽

pp. 205-210 ◽

Cited By ~ 9

Author(s):

Yang Cao ◽

Xun Cao ◽

Xiao-Min Liu

Keyword(s):

L Cells ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Stimulation Of

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.5.g925 ◽

2000 ◽

Vol 279 (5) ◽

pp. G925-G930 ◽

Cited By ~ 76

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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