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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胰岛素、儿茶酚胺、甲状腺激素、生长激素和其它试剂调节分离的大鼠和兔脂肪细胞的代谢。重点放在调节脂肪中的脂质代谢组织. 正在调查的具体领域包括： 1. 环磷酸腺苷的积累与脂肪分解的关系及其对脂肪代谢的影响通过儿茶酚胺，甲状腺激素，糖皮质激素和生长激素。百日咳毒素将被用作一种工具来观察抑制性鸟嘌呤核苷酸结合的作用蛋白质（Ni）在激素的作用。我们特别感兴趣的是百日咳毒素恢复环腺苷酸反应性的机制甲状腺功能减退大鼠的脂肪细胞去甲肾上腺素或毛喉素，纠正脂肪分解的缺陷。儿茶酚胺刺激三酰甘油脂肪酶磷酸化将与环AMP 在脂肪细胞中响应于儿茶酚胺的积累和脂解，甲状腺功能减退、甲状腺功能正常和甲状腺功能亢进大鼠脂肪细胞中的毛喉素。 2. 磷脂酰肌醇转换与胰岛素和α-胰岛素的关系 1脂肪细胞中的儿茶酚胺激动剂作用及其机制百日咳毒素阻断α 1肾上腺素能激活磷脂酰肌醇将对营业额进行调查。将搜索以下条件：其中磷脂酰肌醇分解的活化可以在脂肪细胞，特别是磷脂酰肌醇4，5-二磷酸，激素添加后的前30秒。还将尝试证明在预标记的细胞中磷酸肌醇分解的正常激活脂肪细胞质膜组分。这些研究旨在提供脂质代谢紊乱疾病的基本信息，如糖尿病和动脉粥样硬化。