Tomkin Gerald H
Diabetes Institute of Ireland, Beacon Clinic Dublin, and Blackrock Clinic Dublin, Department of Medicine, Trinity College, Dublin, Ireland.
Atheroscler Suppl. 2008 Sep;9(2):27-32. doi: 10.1016/j.atherosclerosissup.2008.05.012. Epub 2008 Aug 6.
The chylomicron influences very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) composition but itself is atherogenic. Thus abnormalities of chylomicron production are of interest particularly in conditions such as diabetes which confer major cardiovascular risk. Intestinal function is abnormal in diabetes and is a major cause of the dyslipidaemia found in this condition. Studies have suggested that cholesterol absorption is decreased in diabetes and cholesterol synthesis increased. Molecular mechanisms involved in insulin resistance in the intestine and its effect on cholesterol homeostasis in diabetes are described. Abnormalities in triglyceride synthesis and alterations genes regulating cholesterol absorption and intestinal synthesis are discussed. In particular, increase in apolipoprotein B48 synthesis has been demonstrated in animal models of diabetes and insulin resistance. Intestinal mRNA expression of Niemann Pick C1-like 1, protein is increased in both experimental and human diabetes suggesting that an increase in cholesterol transportation does occur. mRNA expression of the ATP binding cassette proteins (ABC) G5 and G8, two proteins working in tandem to excrete cholesterol have been shown to be decreased suggesting increased delivery of cholesterol for absorption. Expression of microsomal triglyceride transfer protein, which assembles the chylomicron particle, is increased in diabetes leading to increase in both number and cholesterol content. In conclusion, diabetes is associated with considerable dysfunction of the intestine leading to abnormal chylomicron composition which may play a major part in the premature development of atherosclerosis.
乳糜微粒会影响极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）的组成，但其本身具有致动脉粥样硬化性。因此，乳糜微粒生成异常尤其在如糖尿病这类具有重大心血管风险的疾病中备受关注。糖尿病患者的肠道功能异常，这是该疾病中血脂异常的主要原因。研究表明，糖尿病患者的胆固醇吸收减少而胆固醇合成增加。本文描述了肠道中胰岛素抵抗的分子机制及其对糖尿病患者胆固醇稳态的影响。还讨论了甘油三酯合成异常以及调节胆固醇吸收和肠道合成的基因改变。特别是，在糖尿病和胰岛素抵抗的动物模型中已证实载脂蛋白B48合成增加。在实验性糖尿病和人类糖尿病中，尼曼匹克C1样1蛋白的肠道mRNA表达均增加，这表明胆固醇转运确实增加。已显示协同作用以排泄胆固醇的两种ATP结合盒蛋白（ABC）G5和G8的mRNA表达降低，这表明用于吸收的胆固醇递送增加。组装乳糜微粒颗粒的微粒体甘油三酯转移蛋白的表达在糖尿病中增加，导致数量和胆固醇含量均增加。总之，糖尿病与肠道的相当大功能障碍相关，导致乳糜微粒组成异常，这可能在动脉粥样硬化的过早发展中起主要作用。
