VERY-LOW DENSITY LIPOPROTEIN METABOLISM IN DIABETES

糖尿病中的极低密度脂蛋白代谢

• 批准号: 3471109
• 负责人: DAVID W GARBER
• 金额: $ 9.16万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3471109
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein metabolism; densitometry; diabetes mellitus; disease /disorder model; drug related diabetes mellitus; glycosylation; high performance liquid chromatography; hormone regulation /control mechanism; insulin; laboratory rat; lipoprotein lipase; liver metabolism; radiotracer; streptozotocin; thyroid hormones; very low density lipoprotein

Diabetes mellitus is associated with an increased risk of atherosclerosis that may be associated with alterations in lipid metabolism. The overall objective of this study is to determine the effects of experimentally-induced diabetes mellitus on very-low-density-lipoprotein (VLDL) metabolism in the rat. In order to accomplish this objective, the following specific aims will be pursued: 1) Clearance of 125I-VLDL apolipoproteins by diabetic and control rats will be measured in vivo and in isolated liver perfusions. In particular, the presence or absence of selective clearance of either of the predominant forms of apolipoprotein B will be determined. 2) The involvement of insulin and thyroid hormones in the control of apolipoprotein clearance in diabetics will be investigated. 3) The degree of glycosylation of apolipoproteins from diabetic animals will be measured, and the effects of glycosylation on apolipoprotein clearance will be determined. 4) Activity of lipoprotein lipase and hepatic lipase will be measured in diabetic rats. The effects of glycosylation of apolipoproteins on lipoprotein lipase and hepatic lipase activities will be investigated. The model of diabetes to be used in these experiments will be the streptozotocin-diabetic rat. Diabetes will be induced by injection of streptozotocin at a dose of 65 mg/kg body weight. Rats will be maintained on insulin for one week in order to minimize direct toxic effects of streptozotocin, then insulin will be withdrawn for at least 3 days prior to any experimental procedures.

糖尿病与动脉粥样硬化的风险增加有关 这可能与脂质代谢的改变有关。 总体 这项研究的目的是确定 实验诱导的糖尿病在非常低密度脂蛋白上 （VLDL）大鼠的代谢。 为了实现这一目标， 将追求以下特定目标：1）清除125i-vldl 糖尿病和对照大鼠的载脂蛋白将在体内测量 在孤立的肝脏灌注中。 特别是，存在或不存在 选择性清除两种主要形式的载脂蛋白B 将确定。 2）胰岛素和甲状腺激素参与 将研究糖尿病患者载脂蛋白清除率的控制。 3）糖尿病动物的载脂蛋白的糖基化程度 将测量，以及糖基化对载脂蛋白的影响 清除将被确定。 4）脂蛋白脂肪酶和 肝脂肪酶将在糖尿病大鼠中测量。 效果 脂蛋白脂肪酶和肝脂肪酶对载脂蛋白的糖基化 活动将进行调查。 在这些中使用的糖尿病模型 实验将是链蛋白酶 - 糖尿病大鼠。 糖尿病会 以65 mg/kg体重的剂量注射链霉菌素。 大鼠将在胰岛素上维持一周，以最大程度地减少直接 链蛋白酶的毒性作用，然后将胰岛素撤回 在任何实验程序之前至少3天。