Levy E, Shafrir E, Ziv E, Bar-On H
Biochim Biophys Acta. 1985 May 17;834(3):376-85. doi: 10.1016/0005-2760(85)90011-6.
Tri[14C]acylglycerol-labelled chylomicrons, obtained from cannulated mesenteric lymph of streptozotocin-diabetic donor rats, when intravenously injected into non-diabetic recipient rats, disappeared from the circulation at a significantly slower rate than similarly prepared tri[14C]acylglycerol chylomicrons from non-diabetic donor rats (t1/2, 5.6 +/- 0.7 vs. 3.2 +/- 0.5 min-1, P less than 0.02). The appearance of labelled lipolysis products among plasma lipids (free fatty acid, cholesterol ester and phospholipid fractions) was delayed, indicating decreased availability for lipolysis of the chylomicron-borne triacylglycerol of diabetic origin. Tissue distribution of triacylglycerol, 15 min after the injection of chylomicrons to recipient rats, disclosed a 4-5-fold increase in uptake by muscles (heart and diaphragm) in relation to adipose tissues (epididymal and perirenal sites), in the case of chylomicrons of diabetic derivation. Since a large share of the chylomicron triacylglycerol was taken up by the liver, this tissue was perfused with chylomicron 'remnants' prepared by partial in vitro lipolysis with purified lipoprotein lipase. The 'remnants' of diabetic derivation were taken up by the liver at a 2-3-fold slower rate than those of non-diabetic origin. Chylomicrons derived from diabetic rats were found to be similar in size but markedly depleted of E apolipoproteins as determined by SDS-polyacrylamide gel electrophoresis, isoelectric focussing and a specific immunoassay. Decreases were also seen in A-I apolipoproteins by immunoassay and isoelectric focussing. Chylomicron 'remnants' were also markedly apolipoprotein E-deficient. In vitro incubation of the 'diabetic remnants' with high-density lipoproteins raised their apolipoprotein E content approx. 3-fold and considerably increased their hepatic uptake. Injection of intact chylomicrons preincubated with high-density lipoproteins likewise increased their in vivo removal rate toward the range of that of 'non-diabetic' chylomicrons. We conclude that diabetes-induced changes in the apolipoprotein composition of the chylomicrons and chylomicron remnants play an important role in their removal from the circulation. It appears that their recognition pattern is altered, reducing their ability to interact with receptor sites in the peripheral tissues and the liver, respectively.
从链脲佐菌素诱导的糖尿病供体大鼠的插管肠系膜淋巴中获得的三[14C]酰基甘油标记的乳糜微粒，静脉注射到非糖尿病受体大鼠体内后，其从循环中消失的速度明显慢于来自非糖尿病供体大鼠的类似制备的三[14C]酰基甘油乳糜微粒（半衰期分别为5.6±0.7和3.2±0.5分钟-1，P<0.02）。血浆脂质（游离脂肪酸、胆固醇酯和磷脂部分）中标记的脂解产物的出现延迟，表明糖尿病来源的乳糜微粒携带的三酰基甘油的脂解可用性降低。在向受体大鼠注射乳糜微粒15分钟后，三酰基甘油的组织分布显示，与脂肪组织（附睾和肾周部位）相比，糖尿病来源的乳糜微粒使肌肉（心脏和膈肌）的摄取增加了4-5倍。由于乳糜微粒三酰基甘油的很大一部分被肝脏摄取，因此用纯化的脂蛋白脂肪酶进行部分体外脂解制备的乳糜微粒“残余物”灌注该组织。糖尿病来源的“残余物”被肝脏摄取的速度比非糖尿病来源的慢2-3倍。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳、等电聚焦和特异性免疫测定发现，糖尿病大鼠来源的乳糜微粒大小相似，但E载脂蛋白明显减少。通过免疫测定和等电聚焦也发现A-I载脂蛋白减少。乳糜微粒“残余物”也明显缺乏载脂蛋白E。将“糖尿病残余物”与高密度脂蛋白进行体外孵育，可使它们的载脂蛋白E含量增加约3倍，并显著增加它们被肝脏的摄取。注射与高密度脂蛋白预孵育的完整乳糜微粒同样会提高它们在体内的清除率，使其接近“非糖尿病”乳糜微粒的清除率范围。我们得出结论，糖尿病引起的乳糜微粒和乳糜微粒残余物载脂蛋白组成的变化在它们从循环中清除的过程中起重要作用。似乎它们的识别模式发生了改变，分别降低了它们与外周组织和肝脏中的受体位点相互作用的能力。
