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孕酮和合成类固醇在雌性大鼠脂肪细胞的受体后水平产生胰岛素抵抗。

Progesterone and synthetic steroids produce insulin resistance at the post-receptor level in adipocytes of female rats.

作者信息

Sutter-Dub M T, Kaaya A, Sfaxi A l, Sodoyez-Goffaux F, Sodoyez J C, Sutter B C

机构信息

Department of Endocrinology, Université de Bordeaux I, France.

出版信息

Steroids. 1988 Nov-Dec;52(5-6):583-608. doi: 10.1016/0039-128x(88)90125-0.

DOI:10.1016/0039-128x(88)90125-0
PMID:3076030
Abstract

The effects of progesterone, its agonists (progestin RU-5020, glucocorticoid RU-26988) and antagonist (antiprogesterone, anti-glucocorticoid RU-486) were tested on isolated fat cells in vitro. When added to the incubation medium, all four steroids decreased basal glucose oxidation. The inhibitory effect of the steroids appeared early (20 min incubation) and was sustained during a 2-h incubation. The early inhibitory effect was less marked for progesterone agonist RU-5020 than for the other three steroids. When incubation was prolonged for 2 h, the lowest inhibitory effect was observed with progesterone antagonist RU-486. Insulin-stimulated glucose oxidation was inhibited by progesterone, its antagonist RU-486, one of its agonists RU-26988, but not by the other agonist RU-5020. Analysis of the dose response curves showed that progesterone, RU-26988, and RU-486 decreased fat cells' responsiveness and, only for RU-486, sensitivity to insulin. Adipocytes isolated from ovariectomized, progesterone-treated rats showed a decreased maximal response to insulin and decreased insulin sensitivity in opposition to cells incubated directly with the steroid. No inhibition of 125I-labeled insulin binding was seen as an acute or chronic effect of progesterone. It is concluded that progesterone and the studied related steroids decrease glucose oxidation by mechanism(s) distal to insulin binding to its specific receptors.

摘要

在体外对分离的脂肪细胞测试了孕酮及其激动剂(孕激素RU - 5020、糖皮质激素RU - 26988)和拮抗剂(抗孕激素、抗糖皮质激素RU - 486)的作用。当添加到孵育培养基中时,所有这四种类固醇均降低基础葡萄糖氧化。类固醇的抑制作用出现较早(孵育20分钟),并在2小时的孵育过程中持续存在。对于孕酮激动剂RU - 5020,其早期抑制作用不如其他三种类固醇明显。当孵育延长至2小时时,观察到孕酮拮抗剂RU - 486的抑制作用最低。胰岛素刺激的葡萄糖氧化受到孕酮、其拮抗剂RU - 486、其激动剂之一RU - 26988的抑制,但不受另一种激动剂RU - 5020的抑制。剂量反应曲线分析表明,孕酮、RU - 26988和RU - 486降低了脂肪细胞对胰岛素的反应性,且仅对于RU - 486而言,降低了对胰岛素的敏感性。从卵巢切除并用孕酮处理的大鼠分离的脂肪细胞,与直接用该类固醇孵育的细胞相反,对胰岛素的最大反应降低且胰岛素敏感性降低。未观察到125I标记的胰岛素结合受孕酮急性或慢性作用的抑制。结论是,孕酮及所研究的相关类固醇通过胰岛素与其特异性受体结合的下游机制降低葡萄糖氧化。

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