HORMONAL CONTROL OF LIPID METABOLISM

脂质代谢的激素控制

• 批准号: 3235464
• 负责人: JOHN N FAIN
• 金额: $ 15.57万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3235464
• 关键词: adenylate cyclase; adipocytes; alpha antiadrenergic agent; atherosclerosis; bacterial toxins; catecholamines; cyclic AMP; diacylglycerols; gel electrophoresis; glucocorticoids; glucose metabolism; guanine nucleotides; hormone regulation /control mechanism; hypothyroidism; insulin; lipid metabolism; lipolysis; norepinephrine; pertussis vaccine; phosphatidylinositols; somatotropin; thyroid hormones; triacylglycerol lipase

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这些机制。 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新陈代谢。 重点是脂肪中脂代谢的调节。 组织。正在调查的具体领域包括： 1.环磷酸腺苷蓄积与脂解作用的关系 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 研究鸟嘌呤核苷酸结合抑制作用的工具 荷尔蒙作用中的蛋白质(镍)。我们特别感兴趣的是 百日咳毒素恢复环磷酸腺苷反应性的机制 甲状腺功能低下大鼠脂肪细胞对去甲肾上腺素或Forsklin的影响 纠正脂肪分解的缺陷。儿茶酚胺对中枢神经系统的刺激作用 三酰甘油脂肪酶磷酸化与环磷酸腺苷相关 儿茶酚胺和安非他明对脂肪细胞的蓄积和脂解作用 甲状腺功能减退、甲状腺功能正常和甲亢大鼠脂肪细胞中的Forsklin。 2.磷脂酰肌醇转换率与胰岛素、α的关系 1儿茶酚胺在脂肪细胞中的激动剂作用及其机制 百日咳毒素阻断磷脂酰肌醇的α1肾上腺素能激活 将对营业额进行调查。将搜索以下条件： 磷脂酰肌醇分解的激活可见于 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 演示磷脂酰肌醇在预标记物中的正常激活 脂肪细胞质膜组分。这些研究旨在提供 有关脂代谢紊乱疾病的基本信息，如 糖尿病和动脉粥样硬化。