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 Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein-Coupled Receptor FFAR2

Diabetes ◽  
2011 ◽  
Vol 61 (2) ◽  
pp. 364-371 ◽  
Author(s):  
G. Tolhurst ◽  
H. Heffron ◽  
Y. S. Lam ◽  
H. E. Parker ◽  
A. M. Habib ◽  
...  
Keyword(s):  
Fatty Acids ◽  
G Protein ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
G Protein Coupled Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Chain Fatty Acids

Gentiana scabra extracts stimulate glucagon-like peptide-1 secretion via G protein-coupled receptor pathway

2012 ◽  
Vol 6 (2) ◽  
pp. 114-119 ◽  
Author(s):  
Min-Hee Shin ◽  
Hyo-Weon Suh ◽  
Ki-Beom Lee ◽  
Ki-Suk Kim ◽  
Hea Jung Yang ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Gentiana Scabra ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

scholarly journals GRK Inhibition Potentiates Glucagon-Like Peptide-1 Action

2021 ◽  
Vol 12 ◽  
Author(s):  
Seunghun P. Lee ◽  
Jenson Qi ◽  
Guozhang Xu ◽  
Matthew M. Rankin ◽  
James Littrell ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Dipeptidyl Peptidase 4 ◽  
Receptor Kinases ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Receptor Interacting Proteins ◽  
G Protein Coupled

The glucagon-like peptide-1 receptor (GLP-1R) is a G-protein-coupled receptor (GPCR) whose activation results in suppression of food intake and improvement of glucose metabolism. Several receptor interacting proteins regulate the signaling of GLP-1R such as G protein-coupled receptor kinases (GRK) and β-arrestins. Here we evaluated the physiological and pharmacological impact of GRK inhibition on GLP-1R activity leveraging small molecule inhibitors of GRK2 and GRK3. We demonstrated that inhibition of GRK: i) inhibited GLP-1-mediated β-arrestin recruitment, ii) enhanced GLP-1-induced insulin secretion in isolated islets and iii) has additive effect with dipeptidyl peptidase 4 in mediating suppression of glucose excursion in mice. These findings highlight the importance of GRK to modulate GLP-1R function in vitro and in vivo. GRK inhibition is a potential therapeutic approach to enhance endogenous and pharmacologically stimulated GLP-1R signaling.

Lateral Allosterism in the Glucagon Receptor Family: Glucagon-Like Peptide 1 Induces G-Protein-Coupled Receptor Heteromer Formation

2011 ◽  
Vol 81 (3) ◽  
pp. 309-318 ◽  
Author(s):  
Dominik Schelshorn ◽  
Fanny Joly ◽  
Sophie Mutel ◽  
Cornelia Hampe ◽  
Billy Breton ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Glucagon Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Receptor Family

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

1995 ◽  
Vol 145 (3) ◽  
pp. 521-526 ◽  
Author(s):  
P Plaisancié ◽  
V Dumoulin ◽  
J-A Chayvialle ◽  
J-C Cuber
Keyword(s):  
Bile Acids ◽  
Total Concentration ◽  
Gum Arabic ◽  
Secretory Activity ◽  
Short Chain Fatty Acids ◽  
Rat Colon ◽  
Maximal Response ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

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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