Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal.
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.
Yang
Li
L
Department of Forensic Sciences, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
Li
Xiaoming
X
Ji
Yong
Y
Kohan
Alison B
AB
Wang
David Q-H
DQ
Howles
Philip N
PN
Hui
David Y
DY
Lai
Jianghua
J
Tso
Patrick
P
D000704:Analysis of Variance; D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D019422:Dietary Sucrose / Q000008:administration & dosage; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D000069438:Ezetimibe; D005526:Food, Formulated; D005749:Gastric Inhibitory Polypeptide / Q000032:analysis / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000032:analysis / Q000378:metabolism*; D007408:Intestinal Absorption; D008196:Lymph / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001384:Azetidines; D019422:Dietary Sucrose; C082131:Ensure formulated food; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D002784:Cholesterol; D000069438:Ezetimibe