VERY-LOW DENSITY LIPOPROTEIN METABOLISM IN DIABETES

糖尿病中的极低密度脂蛋白代谢

• 批准号: 3471107
• 负责人: DAVID W GARBER
• 金额: $ 7.8万
• 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/3471107
• 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be maintained on insulin for one week in order to minimize direct toxic effects of streptozotocin, then insulin will be withdrawn for at least 3 days prior to any experimental procedures.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风险增加有关 这可能与脂质代谢的改变有关。 整体 这项研究的目的是确定的影响 极低密度脂蛋白实验诱发的糖尿病 (VLDL) 在大鼠中的代谢。 为了实现这一目标， 将追求以下具体目标： 1) 清除 125I-VLDL 将在体内测量糖尿病大鼠和对照大鼠的载脂蛋白 在孤立的肝脏灌注中。 特别是，存在或不存在 选择性清除载脂蛋白 B 的任一主要形式 将被确定。 2）胰岛素和甲状腺激素的参与 将研究糖尿病患者载脂蛋白清除率的控制。 3) 糖尿病动物载脂蛋白的糖基化程度 将进行测量，以及糖基化对载脂蛋白的影响 清关将被确定。 4) 脂蛋白脂肪酶的活性和 将测量糖尿病大鼠的肝脂肪酶。 的影响 载脂蛋白在脂蛋白脂肪酶和肝脂肪酶上的糖基化 活动将受到调查。 用于这些的糖尿病模型 实验将是链脲佐菌素糖尿病大鼠。 糖尿病将会 通过注射链脲佐菌素以65mg/kg体重的剂量诱导。 大鼠将维持使用胰岛素一周，以尽量减少直接 链脲佐菌素的毒性作用，则将停用胰岛素至少 任何实验程序前至少 3 天。