scholarly journals Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells

2018 ◽  
Vol 7 ◽  
pp. 90-101 ◽  
Author(s):  
Deborah A. Goldspink ◽  
Van B. Lu ◽  
Lawrence J. Billing ◽  
Pierre Larraufie ◽  
Gwen Tolhurst ◽  
...  
Keyword(s):  
Bile Acids ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

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 Importance of Large Intestine in Regulating Bile Acids and Glucagon-Like Peptide-1 in Germ-Free Mice

2015 ◽  
Vol 43 (10) ◽  
pp. 1544-1556 ◽  
Author(s):  
Felcy Pavithra Selwyn ◽  
Iván L. Csanaky ◽  
Youcai Zhang ◽  
Curtis D. Klaassen
Keyword(s):  
Bile Acids ◽  
Large Intestine ◽  
Germ Free ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Bile-induced secretion of glucagon-like peptide-1: pathophysiological implications in type 2 diabetes?

2010 ◽  
Vol 299 (1) ◽  
pp. E10-E13 ◽  
Author(s):  
Filip K. Knop
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Secretion ◽  
Postprandial Glucose ◽  
Glucose Lowering ◽  
Incretin Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

During the last decades it has become clear that bile acids not only act as simple fat solubilizers, but additionally represent complex hormonal metabolic integrators. Bile acids activate both nuclear receptors (controlling transcription of genes involved in for example bile acid, cholesterol, and glucose metabolism) and the cell surface G protein-coupled receptor TGR5 (modulating energy expenditure in brown fat and muscle cells). It has been shown that TGR5 is expressed in enteroendocrine L cells, which secrete the potent glucose-lowering incretin hormone glucagon-like peptide-1 (GLP-1). Recently it was shown that bile acid-induced activation of TGR5 results in intestinal secretion of GLP-1 and that enhanced TGR5 signaling improves postprandial glucose tolerance in diet-induced obese mice. This Perspectives article presents these novel findings in the context of prior studies on nutrient-induced GLP-1 secretion and outlines the potential implications of bile acid-induced GLP-1 secretion in physiological, pathophysiological, and pharmacological perspectives.

scholarly journals A Surgical Model in Male Obese Rats Uncovers Protective Effects of Bile Acids Post-Bariatric Surgery

Endocrinology ◽  
2013 ◽  
Vol 154 (7) ◽  
pp. 2341-2351 ◽  
Author(s):  
Rohit Kohli ◽  
Kenneth DR Setchell ◽  
Michelle Kirby ◽  
Andriy Myronovych ◽  
Karen K. Ryan ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Bile Acid ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Bile Acids ◽  
Hepatic Steatosis ◽  
Homologous Protein ◽  
Obese Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Bariatric surgery elevates serum bile acids. Conjugated bile acid administration, such as tauroursodeoxycholic acid (TUDCA), improves insulin sensitivity, whereas short-circuiting bile acid circulation through ileal interposition surgery in rats raises TUDCA levels. We hypothesized that bariatric surgery outcomes could be recapitulated by short circuiting the normal enterohepatic bile circulation. We established a model wherein male obese rats underwent either bile diversion (BD) or Sham (SH) surgery. The BD group had a catheter inserted into the common bile duct and its distal end anchored into the middistal jejunum for 4–5 weeks. Glucose tolerance, insulin and glucagon-like peptide-1 (GLP-1) response, hepatic steatosis, and endoplasmic reticulum (ER) stress were measured. Rats post-BD lost significantly more weight than the SH rats. BD rats gained less fat mass after surgery. BD rats had improved glucose tolerance, increased higher postprandial glucagon-like peptide-1 response and serum bile acids but less liver steatosis. Serum bile acid levels including TUDCA concentrations were higher in BD compared to SH pair-fed rats. Fecal bile acid levels were not different. Liver ER stress (C/EBP homologous protein mRNA and pJNK protein) was decreased in BD rats. Bile acid gavage (TUDCA/ursodeoxycholic acid [UDCA]) in diet-induced obese rats, elevated serum TUDCA and concomitantly reduced hepatic steatosis and ER stress (C/EBP homologous protein mRNA). These data demonstrate the ability of alterations in bile acids to recapitulate important metabolic improvements seen after bariatric surgery. Further, our work establishes a model for focused study of bile acids in the context of bariatric surgery that may lead to the identification of therapeutics for metabolic disease.

Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients

2013 ◽  
Vol 304 (4) ◽  
pp. G413-G419 ◽  
Author(s):  
David P. Sonne ◽  
Kristine J. Hare ◽  
Pernille Martens ◽  
Jens F. Rehfeld ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Bile Acids ◽  
Plasma Concentrations ◽  
Gut Hormones ◽  
Postprandial Glucose ◽  
Gallbladder Emptying ◽  
Liquid Meal ◽  
Control Subjects ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.

Duodenal-jejunal bypass improves diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids

2015 ◽  
Vol 30 (2) ◽  
pp. 308-315 ◽  
Author(s):  
Hideya Kashihara ◽  
Mitsuo Shimada ◽  
Nobuhiro Kurita ◽  
Hirohiko Sato ◽  
Kozo Yoshikawa ◽  
...  
Keyword(s):  
Bile Acids ◽  
Liver Steatosis ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Jejunal Bypass

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

Effects of glucagon-like peptide-1 (GLP-1) on gastric accommodation, emptying and satiety in humans

2001 ◽  
Vol 120 (5) ◽  
pp. A74-A74
Author(s):  
S AROS ◽  
D KIM ◽  
D BURTON ◽  
G THOMFORDE ◽  
A VELLA ◽  
...  
Keyword(s):  
Gastric Accommodation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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