HORMONAL CONTROL OF LIPID METABOLISM

脂质代谢的激素控制

• 批准号: 3235466
• 负责人: JOHN N FAIN
• 金额: $ 18.05万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3235466
• 关键词: G protein; adenylate cyclase; adipocytes; alpha antiadrenergic agent; atherosclerosis; binding proteins; catecholamines; cyclic AMP; diabetes mellitus; diacylglycerols; enzyme mechanism; forskolin; gel electrophoresis; glucocorticoids; glucose metabolism; guanine nucleotides; hamsters; hormone regulation /control mechanism; hypothyroidism; insulin; laboratory rabbit; laboratory rat; lipid metabolism; lipolysis; norepinephrine; pertussis toxin; 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 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是： 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。

项目成果

Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones.

鸟嘌呤核苷酸结合调节蛋白参与激素激活磷脂酶的证据。

• DOI: 10.1096/fasebj.2.10.2838362
• 发表时间: 1988
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Fain,JN;Wallace,MA;Wojcikiewicz,RJ
• 通讯作者: Wojcikiewicz,RJ

Polyamines inhibit phospholipase C-catalysed polyphosphoinositide hydrolysis. Studies with permeabilized GH3 cells.

多胺抑制磷脂酶 C 催化的多磷酸肌醇水解。

• DOI: 10.1042/bj2551015
• 发表时间: 1988
• 期刊: The Biochemical journal
• 作者: Wojcikiewicz,RJ;Fain,JN
• 通讯作者: Fain,JN