Apolipoprotein C subtype distribution in type 2 diabetes mellitus

Plasma lipid levels and apolipoprotein C (apo C) composition of VLDL were investigated in a group of Type 2 diabetic patients at first attendance at the outpatient clinic and before any therapeutic intervention. Patients were distributed into two groups of 26 individuals, normo- and hyperlipidaemic, respectively, and compared with two matched control groups. Normolipidaemic diabetic patients had higher serum triglycerides, VLDL cholesterol, and lower HDL cholesterol than matched normolipidaemic control subjects. While hyperlipidaemic non-diabetic individuals showed increased apo C II and decreased apo C III-1 percentages when compared with normolipidaemic non-diabetic individuals (12.1 +/- 4.9 vs 8.5 +/- 3.2% and 44.0 +/- 6.7 vs 48.1 +/- 7.0%, respectively, mean +/- SD, both with p less than 0.05), the relative distribution of apo C III isoforms and apo C II was similar in both normo- and hyperlipidaemic diabetic patients.     

Atenolol and metoprolol: Comparison of effects on blood pressure and serum lipoproteins,and side effects

Summary Several -blockers increase VLDL-TG and decrease HDL-cholesterol concentrations. The underlying mechanism ist not yet clear. Some studies have suggested that the effect is less pronounced during treatment with selective -blockers. The effects of 2 such drugs, metoprolol 200 mg/day and atenolol 50 mg/day, have been compared in 50 hypertensive patients (WHO Stage I–II), mean age 47 years. Serum lipoproteins were determined in 20 patients before treatment and after treatment with either drug for 3 months. Both drugs were equally effective in reducing blood pressure. After atenolol the initial VLDL-cholesterol concentration of 1.04 mmol/l had not changed, but it rose to 1.29 mmol/l after metoprolol (p<0.05). The HDL-cholesterol concentration 1.42 mmol/l did not fall during atenolol treatment, but during metoprolol there was a small reduction to 1.31 mmol/l (p<0.05). Hyperlipoproteinaemia is common in hypertensive patients, 40% of the present group had hypertriglyceridaemia and 25% had hypercholesterolaemia. Thus, atenolol 50 mg was found not to affect lipoproteins, whereas metoprolol 200 mg increased the VLDL concentration in 75% of the patients.     

人血浆载脂蛋白E的分离纯化及其抗血清制备

用短时间超速离心结合制备性 SDS 聚丙烯酰胺凝胶电泳纯化人血浆 apoE.以此纯品免疫家兔制备了单价兔抗人 apoE 抗血清,与常规方法相比,本法具有操作简单、费用低和提纯周期短等优点,是一种简单实用的方法。     

Novel microsomal triglyceride transfer protein inhibitors

Microsomal triglyceride transfer protein (MTP) mediates triglyceride absorption and chylomicron secretion from the intestine and very-low-density lipoprotein (VLDL) secretion from the liver, by linking lipid molecules with apolipoprotein B (ApoB). Inhibition of MTP reduces the level of all ApoB-containing lipoproteins, including low-density lipoprotein (LDL). High-throughput screening has produced several families of compounds that are effective in vitro and in vivo as MTP inhibitors and some drugs are currently at clinical trial stage. Drugs that inhibit MTP can potentially be very effective in reducing atherosclerotic vascular disease by lowering levels of all the atherogenic lipoproteins. Partial inhibition of MTP by an inhibitor could be particularly useful when combined with other drugs that alter lipid metabolism but marked inhibition of MTP could cause significant adverse effects.     

极低密度脂蛋白对小鼠腹腔巨噬细胞载脂蛋白E基因表达的影响

为研究载脂蛋白Ｅ含量不同的极低密度脂蛋白对巨噬细胞载脂蛋白Ｅ表达的影响，以肝素－琼脂糖凝胶亲和层析法将正常人极低密度脂蛋白分离为富含载脂蛋白Ｅ和贫含载脂蛋白Ｅ的二种不同亚组分，并分别以不同浓度与小鼠腹腔巨噬细胞共培养。     

高甘油三酯血清对牛主动脉内皮细胞一氧化氮合酶基因表达的影响及其机制的研究

目的研究高甘油三酯血清(HTS)对原代牛主动脉内皮细胞(BVEC)一氧化氮合酶(eNOS)基因表达的影响及其可能机制。方法采用Western印迹法从蛋白质水平检测高甘油三酯血清对牛主动脉内皮细胞eNOS和一氧化氮(NO)活性的影响。在证实其效应的基础上,采用Western印迹法检测经HTS作用后,PKC-MAPK-MAPKK信号转导通路的改变。进一步从Ⅳ型高脂蛋白血症血浆提取极低密度脂蛋白(VLDL)(HTG-VLDL)并采用Western印迹法研究HTG-VLDL对eNOS的蛋白质表达的影响。结果HTS以浓度依赖的方式抑制eNOS的蛋白质表达,减少一氧化氮的产生,并以剂量和时间依赖的方式促进MAPK的磷酸化,而经PKC、MAPKK和MAPK抑制剂预处理后,HTS对eNOS的蛋白质表达的抑制作用更明显;另外发现HTG-VLDL可抑制eNOS的蛋白质表达水平。结论HTS抑制eNOS的蛋白质表达水平,可能部分通过HTG-VLDL对eNOS的影响,但未经PKC-MAPKK-MAPK通路,而且PKC-MAPKK-MAPK可能参与了eNOS正常的蛋白质表达,HTS增加MAPK的磷酸化水平有可能是一种细胞自身保护机制。     

Lipoprotein lipase activity of adipose tissue and skeletal muscle in insulin-deficient human diabetes

Summary We have previously shown that lipoprotein lipase (LPL) activity of tissues is an important determinant not only of plasma VLDL levels but also of HDL-cholesterol. Studies were designed to investigate whether the serum lipoprotein alterations in uncontrolled insulin-deficient diabetes can be accounted for by changes in LPL activity of tissues. The heparin-releasable LPL activity was determined from biopsy samples of adipose tissue and skeletal muscle in 16 patients with newly detected untreated insulin-deficient diabetes and in 16 age-, sex- and body weight-matched healthy control subjects. Repeat assays were carried out after the patients had been on insulin treatment for an average of two weeks and when the diabetes was well controlled. When untreated the patients had increased concentrations of triglycerides and cholesterol in whole serum and in VLDL and LDL while the HDL cholesterol level was lower than that of controls (p<0.01). The cholesterol/triglyceride ratio in each of the three lipoproteins was similar in patients and controls. While untreated the diabetic patients had significantly reduced mean LPL activity both in adipose tissue (average 34% of control mean, p<0.001) and in skeletal muscle (average 45% of control mean, p<0.05). In the whole group HDL-cholesterol was positively correlated with adipose tissue LPL activity (r=+0.58, p<0.001) while log serum total triglyceride and log VLDL-triglyceride showed significant negative correlations with LPL activity of both adipose tissue and skeletal muscle. After initiation of insulin treatment the LPL activity increased significantly (p<0.01) in both tissues but was still subnormal after 2 weeks. At the same time the VLDL and LDL concentrations had returned to normal while the HDL-cholesterol remained low. The results suggest that the increase of VLDL and LDL triglyceride and the decrease of HDL-cholesterol present in uncontrolled insulin-deficient diabetes are, at least partly, accounted for by decreased LPL activity of tissues. The restoration of tissue LPL and of serum HDL-cholesterol by insulin are relatively slow processes. The results are consistent with the hypothesis that HDL-cholesterol concentration is dependent on the efficiency of removal of triglyceride-rich lipoproteins from the circulation.     

Total automated method for determination of cholesterol concentration in high density lipoprotein by heparin-magnesium-albumin precipitation

We describe an automated procedure for determination of high-density-lipoprotein cholesterol in serum by use of heparin-MgCl₂-albumin reagent. ‘AutoAnalyzer’ II equipment was used in which high-density lipoprotein was separated from precipitate containing very-low and low-density lipoproteins by filtering on-line across a cellulose acetate membrane. Cholesterol concentration was measured by the enzymic method of Allain. Good correlation was obtained using the automated method compared to the heparin-MgCl₂-albumin (r = 0.99) or sodium phosphotungstate-MgCl₂ procedure (r = 0.97). Contamination was minimal with a contamination coefficient lower than 2.5%. The method presented was linear (0 to 2.50 mmol/l) and could be applied to lipemic samples with a coefficient of variation better than 3%. This study showed thus that this new procedure was suitable for routine work with a good rate (60 samples/h) in almost any laboratory.     

The effects of chlorpropamide and insulin on serum lipids,lipoproteins and fractional triglyceride removal

Summary The effects of chlorpropamide on serum lipids, lipoproteins and fractional triglyceride removal have been studied over 12 months on 10 maturity onset diabetics not controlled on diet alone. Similar studies were carried out in 6 maturity onset diabetics who had failed to respond to sulphonylureas and 6 new insulin requiring diabetics. In the chlorpropamide treated patients there was an initial fall in serum and VLDL triglyceride but this effect was lost at 12 months. There was no change in fractional triglyceride removal. At 12 months there was a fall in LDL and a rise in HDL cholesterol. An initial improvement in glucose tolerance and insulin secretion was maintained at 12 months.In the insulin treated group the initial fall in serum and VLDL triglyceride was maintained at 12 months and was accompanied by an increase in fractional triglyceride removal. There was also a fall in LDL and a rise in HDL cholesterol at 12 months.The failure of chlorpropamide to maintain the reduction in serum and VLDL triglyceride could be of importance in the genesis of coronary heart disease in maturity onset diabetics. The fall in LDL and rise in HDL cholesterol found both with chlorpropamide and insulin might be beneficial.