Lipid metabolism in hyperinsulinemia and insulin resistance and atheroscleorosis

1.大鼠外源性高胰岛素血症：高胰岛素血症促进动脉粥样硬化形成的机制尚不清楚。每日皮下注射胰岛素锌混悬液12周，观察高胰岛素血症对动脉粥样硬化危险因素的影响。高胰岛素血症确实是胆固醇酯和甘油三酯的沉积，特别是含有单不饱和脂肪酸的胆固醇和甘油三酯的沉积，以及低密度脂蛋白和组织中花生四烯酸的异常分布。高果糖饮食引起的高胰岛素血症大鼠在两周的喂养中，40%果糖和7%猪油饮食导致胰岛素抵抗并伴有高血压。骨骼肌甘油三酯的脂肪酸组成表明，饱和脂肪酸和单不饱和脂肪酸的比例较高，多不饱和脂肪酸的比例较低。苯扎贝特，而不是普罗布考，实际上使脂肪酸组成和胰岛素抵抗正常化。低密度脂蛋白颗粒大小和胰岛素由于低密度脂蛋白颗粒大小似乎与缺血性冠状动脉疾病有关，我们评估了胰岛素对210名受试者低密度脂蛋白颗粒大小变化的影响。低密度脂蛋白与高密度脂蛋白胆固醇呈正相关，与胆固醇、甘油三酯、血糖、空腹胰岛素、HbA1c、体重指数呈负相关。作为对75g口服葡萄糖负荷的响应，低密度脂蛋白的大小根据负荷前的大小和胰岛素水平而改变。决定低密度脂蛋白大小的一个遗传因素是载脂蛋白E-ε4等位基因.血管紧张素转换酶I/D基因型与低密度脂蛋白大小无关。

1. Exogenous hyperinsulinemia in rats.The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-zinc suspension for 12 weeks. Hyperinsulinemia indeed deposition of cholesterol esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues.Hyperinsulinemia induced by high-fructose feedings in ratsTwo-weeks feeding of 40% fructose and 7% lard diet resulted in insulin resistance accompanied with high blood pressure in rats. The fatty acid composition of skeletal-muscle triglycerides demonstrated a higher percentage of saturated and monounsaturated fatty acids and a lower percentage of polyunsaturated fatty acids. Bezafibrate, not probucol, virtually normalized the fatty acid composition and insulin resistance.3. LDL particle size and insulinSince LDL particle size appears to be associated with ischemic coronary artery disease, we evaluated the influence of insulin on the variation in LDL particle size in 210 subjects. LDL size was positively correlated with HDL cholesterol, and was inversely correlated with cholesterol, TG, glucose, fasting insulin, Hb A 1c and body mass index. In response to a 75 g oral glucose load, LDL size was changed according to the pre-load size and insulin levels. One genetic factor to determine the LDL size was Apolipoprotein E- ε 4 allete. Angiotensin converting enzyme I/D genotype was not associated with LDL size.