scholarly journals Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal

2010 ◽  
Vol 299 (5) ◽  
pp. G1003-G1011 ◽  
Author(s):  
Li Yang ◽  
Xiaoming Li ◽  
Yong Ji ◽  
Alison B. Kohan ◽  
David Q.-H. Wang ◽  
...  
Keyword(s):  
Intestinal Absorption ◽  
Potent Inhibitor ◽  
Cholesterol Absorption ◽  
Inhibitory Effect ◽  
Enteroendocrine Cells ◽  
Mixed Meal ◽  
Triglyceride Secretion ◽  
Incretin Secretion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Ezetimibe is a potent inhibitor of cholesterol absorption by enterocytes. Although ezetimibe minimally affects the absorption of triglyceride, it is unknown whether ezetimibe affects the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). It has been shown that ezetimibe-treated mice are protected from diet-induced insulin resistance. Since GIP and GLP-1 promote the actions of insulin, we hypothesized that ezetimibe may affect the secretion of GIP and GLP-1 by enteroendocrine cells into lymph in response to the intestinal absorption of a mixed meal (Ensure). To test this hypothesis, we used the lymph fistula rat model to determine GIP and GLP-1 concentrations in lymph during the 2 h after the infusion of Ensure. Ezetimibe significantly reduced lymphatic cholesterol output during fasting, without coincident decreases in glucose, protein, and triglyceride outputs. However, ezetimibe did not influence cholesterol output after infusion of Ensure. Interestingly, ezetimibe significantly reduced the secretion of both GIP and GLP-1 into lymph after the infusion of Ensure. Therefore, the inhibitory effect of ezetimibe on GIP and GLP-1 secretion by enteroendocrine cells occurs outside of the effects of glucose, protein, or triglyceride secretion by the intestine.

Hindbrain glucagon-like peptide-1 receptors (GLP-1R) mediate the eating-inhibitory effect of hepatic portal vein (HPV) GLP-1 infusions

Appetite ◽  
2010 ◽  
Vol 54 (3) ◽  
pp. 668 ◽  
Author(s):  
G. Pacheco-López ◽  
M. Punjabi ◽  
M. Graber ◽  
N. Geary ◽  
M. Arnold ◽  
...  
Keyword(s):  
Portal Vein ◽  
Inhibitory Effect ◽  
Hepatic Portal Vein ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Portal

scholarly journals Exogenous glucagon-like peptide 1 reduces contractions in human colon circular muscle

2014 ◽  
Vol 221 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Antonella Amato ◽  
Sara Baldassano ◽  
Rosa Liotta ◽  
Rosa Serio ◽  
Flavia Mulè
Keyword(s):  
Colonic Motility ◽  
Circular Muscle ◽  
Human Colon ◽  
Inhibitory Effect ◽  
Mechanical Activity ◽  
Organ Bath ◽  
Dependent Manner ◽  
Double Labeling ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 (GLP1) is a naturally occurring peptide secreted by intestinal L-cells. Though its primary function is to serve as an incretin, GLP1 reduces gastrointestinal motility. However, only a handful of animal studies have specifically evaluated the influence of GLP1 on colonic motility. Consequently, the aims of this study were to investigate the effects induced by exogenous GLP1, to analyze the mechanism of action, and to verify the presence of GLP1 receptors (GLP1Rs) in human colon circular muscular strips. Organ bath technique, RT-PCR, western blotting, and immunofluorescence were used. In human colon, exogenous GLP1 reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. This inhibitory effect was significantly reduced by exendin (9–39), a GLP1R antagonist, which per se significantly increased the spontaneous mechanical activity. Moreover, it was abolished by tetrodotoxin, a neural blocker, or Nω-nitro-l-arginine – a blocker of neuronal nitric oxide synthase (nNOS). The biomolecular analysis revealed a genic and protein expression of the GLP1R in the human colon. The double-labeling experiments with anti-neurofilament or anti-nNOS showed, for the first time, that immunoreactivity for the GLP1R was expressed in nitrergic neurons of the myenteric plexus. In conclusion, the results of this study suggest that GLP1R is expressed in the human colon and, once activated by exogenous GLP1, mediates an inhibitory effect on large intestine motility through NO neural release.

Molecular mechanisms underlying nutrient-stimulated incretin secretion

2010 ◽  
Vol 12 ◽  
Author(s):  
Helen E. Parker ◽  
Frank Reimann ◽  
Fiona M. Gribble
Keyword(s):  
Drug Discovery ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Potential Range ◽  
Incretin Hormones ◽  
Appetite Control ◽  
K Cells ◽  
Incretin Secretion ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in the intestinal epithelium in response to nutrient ingestion. The actions of GLP-1 and GIP – not only on local gut physiology but also on glucose homeostasis, appetite control and fat metabolism – have made these hormones an attractive area for drug discovery programmes. The potential range of strategies to target the secretion of these hormones therapeutically has been limited by an incomplete understanding of the mechanisms underlying their release. The use of organ and whole-animal perfusion techniques, cell line models and primary L- and K-cells has led to the identification of a variety of pathways involved in the sensing of carbohydrate, fat and protein in the gut lumen. This review focuses on our current understanding of these signalling mechanisms that might underlie nutrient responsiveness of L- and K-cells.

scholarly journals Effects of meal and incretins in the regulation of splanchnic blood flow

2017 ◽  
Vol 6 (3) ◽  
pp. 179-187 ◽  
Author(s):  
Jukka Koffert ◽  
Henri Honka ◽  
Jarmo Teuho ◽  
Saila Kauhanen ◽  
Saija Hurme ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Disposal ◽  
Mixed Meal ◽  
Organ Specific ◽  
Randomized Intervention ◽  
Glucose Tolerant ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Randomized Intervention Study ◽  
Meal Ingestion

Objective Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions. Design A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed. Methods Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively. Results Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1. Conclusion Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.

A liquid mixed meal or exogenous glucagon-like peptide 1 (GLP-1) do not alter plasma leptin concentrations in healthy volunteers

1997 ◽  
Vol 34 (3) ◽  
pp. 230-234 ◽  
Author(s):  
C. Drewes ◽  
M. A. Nauck ◽  
R. Horn ◽  
J. Holst ◽  
W. Schmiegel ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Mixed Meal ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Plasma Leptin

Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

2001 ◽  
Vol 281 (3) ◽  
pp. G752-G763 ◽  
Author(s):  
Feruze Y. Enç ◽  
Neşe I˙meryüz ◽  
Levent Akin ◽  
Turgut Turoğlu ◽  
Fuat Dede ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Peptide Yy ◽  
Area Under The Curve ◽  
Gut Hormones ◽  
Random Order ◽  
Mixed Meal ◽  
Carbohydrate Absorption ◽  
Plasma Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

We investigated the effect of acarbose, an α-glucosidase and pancreatic α-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 ( r = 0.68 , P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.

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