HORMONAL CONTROL OF LIPID METABOLISM

脂质代谢的激素控制

基本信息

批准号：
3154596
负责人：
JOHN N FAIN
金额：
$ 11.83万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1989-03-31
项目状态：
已结题

项目摘要

The major objectives of the project are the elucidation of the mechanisms by which insulin, catecholamines, thyroid hormones, growth hormone and other agents regulate the metabolism of isolated rat and rabbit fat cells. Emphasis is placed on the regulation of lipid metabolism in adipose tissue. The specific areas being investigated are: 1. The relationship of cyclic AMP accumulation to lipolysis and the regulation of adenylate cyclase by catecholamines, thyroid hormones, glucocorticoids, and growth hormone. Pertussis toxin will be used as a tool to look at the role of the inhibitory guanine nucleotide binding protein (Ni) in the action of hormones. We are especially interested in the mechanisms by which pertussis toxin restores cyclic AMP responsiveness of adipocytes from hypothyroid rats to norepinephrine or forskolin without correcting the defect in lipolysis. Stimulation by catecholamines of triacylglycerol lipase phosphorylation will be correlated with cyclic AMP accumulation and lipolysis in adipocytes in response to catecholamines and forskolin in adipocytes from hypothyroid, euthyroid and hyperthyroid rats. 2. The relationship of phosphatidylinositol turnover to insulin and alpha 1 catecholamine agonist action in adipocytes and the mechanisms by which pertussis toxin blocks alpha1 adrenergic activation of phosphatidylinositol turnover will be investigated. A search will be made for conditions in which activation of phosphatidylinositol breakdown can be seen in adipocytes, especially that of phosphatidylinositol 4,5-bisphosphate during the first 30 sec after hormone addition. An attempt will also be made to demonstrate normonal activation of phosphoinositide breakdown in prelabeled adipocyte plasma membrane fractions. The studies are designed to provide basic information about diseases with disordered lipid metabolism such as diabetes and atherosclerosis.

该项目的主要目标是阐明机制胰岛素，儿茶酚胺，甲状腺激素，生长激素和其他药物调节分离的大鼠和兔脂肪细胞的代谢。重点放在脂肪中脂质代谢的调节上组织。正在研究的特定领域是： 1。环状AMP积累与脂解的关系通过儿茶酚胺，甲状腺激素调节腺苷酸环化酶，糖皮质激素和生长激素。百日咳毒素将用作查看抑制性鸟嘌呤核苷酸结合的作用的工具激素作用中的蛋白质（Ni）。我们对百日咳毒素恢复环状AMP响应的机制从甲状腺功能减退大鼠到去甲肾上腺素或forskolin的脂肪细胞的脂肪细胞纠正脂解的缺陷。刺激儿茶酚胺的刺激三酰基甘油脂肪酶磷酸化将与环状AMP相关脂肪细胞的积累和脂解响应儿茶酚胺和甲状腺功能减退，甲状腺功能亢进和甲状腺功能亢进大鼠的脂肪细胞中的福斯科林。 2。磷脂酰肌醇周转与胰岛素和α的关系 1个儿茶酚胺激动剂在脂肪细胞中的作用及其机制百日咳毒素阻断磷脂酰肌醇的α1肾上腺素能激活营业额将进行调查。搜索条件可以在哪种磷脂酰肌醇分解的激活脂肪细胞，尤其是磷脂酰肌醇4,5-双磷酸酯期间的脂肪细胞添加激素后的前30秒。也将尝试证明预先标签的磷酸肌醇分解的正常激活脂肪细胞质膜分数。研究旨在提供有关脂质代谢无序疾病的基本信息，例如糖尿病和动脉粥样硬化。