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

Yang, Li; Li, Xiaoming; Ji, Yong; Kohan, Alison B.; Wang, David Q.–H.; Howles, Philip N.; Hui, David Y.; Lai, Jianghua; Tso, Patrick

doi:10.1152/ajpgi.00294.2010

Cited by 8 publications

(6 citation statements)

References 53 publications

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“…Ezetimibe was previously reported to reduce or increase active GLP-1 excursion 24,29) , but ezetimibe did not affect active GLP-1 excursion in response to the model meal in this study (Fig. 2j, k, 3j, k).…”

Section: Safety and Tolerabilitycontrasting

confidence: 47%

“…2j, k, 3j, k). Li Yang et al reported that lymphatic incretin was significantly decreased by ezetimibe in a Sprague-Dawley rat model 24) . In contrast, Soo Jin Yang et al reported a reduction in serum dipeptidyl peptidase-4 activity, increased serum active GLP-1, and improved glucose metabolism after ezetimibe treatment in OLETF rats 29) .…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

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Double-Blind Randomized Clinical Trial of the Effects of Ezetimibe on Postprandial Hyperlipidaemia and Hyperglycaemia

Kikuchi

Nezu

Inazumi

et al. 2012

JAT

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Aim: Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 (NPC1L1) and reducing LDL cholesterol (LDL-C). In animals, ezetimibe reversed dietinduced obesity, liver steatosis, and insulin resistance. In humans, its potential effects on liver steatosis and insulin resistance have been suggested. We investigated the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind randomized crossover trial. Methods: Twenty obese men with hypertriglyceridaemia were assigned randomly to an ezetimibe-or a placebo-precedence-treated group. Subjects in the ezetimibe group were treated with ezetimibe (10 mg/day) for the first 4 weeks, followed by a 4-week interval and then treated with placebo for another 4 weeks. The placebo group received these treatments in reverse order. Subjects were requested to fast for at least 12 hours and then received a standard meal. Blood samples were collected at 0, 30, 60, 120, 240, 360 and 480 minutes after the meal on Days 0, 28, 56 and 84 and were used to measure the lipid and glucose metabolism markers. Results: Ezetimibe significantly decreased the postprandial serum triglyceride excursion (p=0.01) and fasting serum LDL-C, remnant-like particles(RLP) and ApoB48 levels (p＜0.05). Postprandial glucose excursion, serum insulin levels, serum glucose-dependent insulinotropic polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) were not significantly affected by ezetimibe treatment. Conclusion: Ezetimibe restored the postprandial dysregulation of lipid but did not affect glucose metabolism in a double-blind randomized crossover trial.

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Section: Safety and Tolerabilitycontrasting

confidence: 47%

Section: Safety and Tolerabilitymentioning

confidence: 99%

Double-Blind Randomized Clinical Trial of the Effects of Ezetimibe on Postprandial Hyperlipidaemia and Hyperglycaemia

Kikuchi

Nezu

Inazumi

et al. 2012

JAT

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“…Rats were anesthetized with isoflurane, then the superior mesenteric lymphatic duct was cannulated with polyvinyl chloride tubing (0.5 mm ID, 0.8 mm OD; Tyco Electronics, Castle Hill, Australia) according to the method of Bollman et al 32 with slight modifications. 43 The lymph cannula was secured with cyanoacrylate glue (Krazy Glue, Columbus, OH). Intraduodenal cannulation was performed by inserting a silicone feeding tube (1.02 mm ID, 2.16 mm OD; VWR International, West Chester, PA) approximately 2 cm beyond the pylorus into the duodenum via a fundal incision of the stomach.…”

Section: Lymph Fistula Surgery and Lymph Collectionmentioning

confidence: 99%

Dual-channel <italic>in-situ</italic> optical imaging system for quantifying lipid uptake and lymphatic pump function

et al. 2012

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Abstract. Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport. The imaging platform provides the capability of dual-channel imaging of both high-speed bright-field video and fluorescence simultaneously. Utilizing post-acquisition image processing algorithms, we can quantify correlations between vessel pump function, lymph flow, and lipid concentration of mesenteric lymphatic vessels in situ. All image analysis is automated with customized LabVIEW virtual instruments; local flow is measured through lymphocyte velocity tracking, vessel contraction through measurements of the vessel wall displacement, and lipid uptake through fluorescence intensity tracking of an orally administered fluorescently labelled fatty acid analogue, BODIPY FL C 16 . This system will prove to be an invaluable tool for scientists studying intestinal lymphatic function in health and disease, and those investigating strategies for targeting the lymphatics with orally delivered drugs to avoid first pass metabolism.

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“…In addition to the increased blood flow in gut, there is an increase in vascular permeability in response to fat absorption. As a result of the increase in mesenteric blood flow and in vascular permeability, gastrointestinal lymphatic flow and composition (such as an increase in protein concentration) also change dramatically during feeding [17,18]. In addition to the prevention of edema, the gastrointestinal lymphatic system is also coupled with other gastrointestinal function (transport of chylomicrons) [19].…”

Section: Events Associated With Fat Absorption In the Small Intestinementioning

confidence: 99%

“…2). Both chylomicrons, containing long-chain fatty acids, and lymphocytes are transported in the mesenteric lymph [19], and lymphatic flow, protein flux, and lymphocyte trafficking all increase dramatically during fat absorption [7,17,18]. Fat absorption also stimulates intestinal immune cells including macrophages and intraepithelial lymphocytes and enterocytes to release cytokines [7–10].…”

Section: Events Associated With Fat Absorption In the Small Intestinementioning

confidence: 99%

Nutrient-induced inflammation in the intestine

Sakata

Tso

2011

Current Opinion in Clinical Nutrition and Metabolic Care

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Purpose of review To review our current understanding of the relationship between absorption of nutrients and intestinal inflammatory response. Recent findings There is increasing evidence linking gut local inflammatory events with the intake of nutrients. Our recent studies, using the conscious lymph fistula rat model, demonstrate that fat absorption activates the intestinal mucosal mast cells. This is accompanied by a dramatic increase in the lymphatic release of mast cell mediators including histamine, rat mucosal mast cell protease II (RMCPII), as well as the lipid mediator prostaglandin D2 (PGD2). Clinical studies suggest that increased consumption of animal fat may play a role in the pathogenesis of inflammatory bowel disease. This impact of dietary fat may not be restricted to the gut but may extend to the whole body. There is evidence linking a high-fat diet-induced metabolic syndrome, with a low-grade chronic inflammatory state. In this review, we hope to convince the readers that fat absorption can have far reaching physiological and pathophysiological consequences. Summary Understanding the relationship between nutrient absorption and intestinal inflammation is important. We need a better understanding of the interaction between enterocytes and the intestinal immune cells in nutrient absorption and the gut inflammatory responses.

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

Abstract: Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal.

Cited by 8 publications

References 53 publications

Double-Blind Randomized Clinical Trial of the Effects of Ezetimibe on Postprandial Hyperlipidaemia and Hyperglycaemia

Double-Blind Randomized Clinical Trial of the Effects of Ezetimibe on Postprandial Hyperlipidaemia and Hyperglycaemia

Dual-channel <italic>in-situ</italic> optical imaging system for quantifying lipid uptake and lymphatic pump function

Nutrient-induced inflammation in the intestine

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