Document Detail


Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal.
MedLine Citation:
PMID:  20651007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Li Yang; Xiaoming Li; Yong Ji; Alison B Kohan; David Q-H Wang; Philip N Howles; David Y Hui; Jianghua Lai; Patrick Tso
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-22
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  299     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-29     Completed Date:  2010-11-12     Revised Date:  2011-11-01    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G1003-11     Citation Subset:  IM    
Affiliation:
Department of Forensic Sciences, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Azetidines / pharmacology*
Cholesterol / analysis,  secretion
Dietary Sucrose / administration & dosage
Enteroendocrine Cells / drug effects*,  secretion*
Enzyme-Linked Immunosorbent Assay
Gastric Inhibitory Polypeptide / analysis,  secretion*
Glucagon-Like Peptide 1 / analysis,  secretion*
Intestinal Absorption*
Lymph / chemistry
Male
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
DK-059630/DK/NIDDK NIH HHS; DK-076907/DK/NIDDK NIH HHS; DK-076928/DK/NIDDK NIH HHS; DK-077170/DK/NIDDK NIH HHS; DK-54012/DK/NIDDK NIH HHS; DK-73917/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Azetidines; 0/Dietary Sucrose; 109320-37-8/Ensure; 163222-33-1/ezetimibe; 57-88-5/Cholesterol; 59392-49-3/Gastric Inhibitory Polypeptide; 89750-14-1/Glucagon-Like Peptide 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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