Department of Forensic Sciences, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
Am J Physiol Gastrointest Liver Physiol. 2010 Nov;299(5):G1003-11. doi: 10.1152/ajpgi.00294.2010. Epub 2010 Jul 22.
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.
依泽替米贝是一种有效的肠细胞胆固醇吸收抑制剂。虽然依泽替米贝对甘油三酯的吸收影响很小，但尚不清楚它是否会影响肠促胰岛素激素葡萄糖依赖性胰岛素释放肽（GIP）和胰高血糖素样肽-1（GLP-1）的分泌。已表明，依泽替米贝处理的小鼠可防止饮食引起的胰岛素抵抗。由于 GIP 和 GLP-1 促进胰岛素的作用，我们假设依泽替米贝可能会影响肠内分泌细胞在混合餐（Ensure）吸收后向淋巴中分泌 GIP 和 GLP-1。为了验证这一假设，我们使用淋巴瘘大鼠模型，在给予 Ensure 后 2 小时内测定淋巴中 GIP 和 GLP-1 的浓度。依泽替米贝在空腹时可显著减少淋巴中的胆固醇输出，而葡萄糖、蛋白质和甘油三酯的输出没有同时减少。然而，依泽替米贝在给予 Ensure 后并不影响胆固醇的输出。有趣的是，依泽替米贝在给予 Ensure 后可显著减少 GIP 和 GLP-1 向淋巴中的分泌。因此，依泽替米贝对肠内分泌细胞分泌 GIP 和 GLP-1 的抑制作用发生在肠道葡萄糖、蛋白质或甘油三酯分泌的作用之外。
