Knutson V P
J Biol Chem. 1986 Aug 5;261(22):10306-12.
The treatment of confluent embryonic Swiss mouse fibroblasts (3T3-C2 cells) with glucocorticoids has been shown to result in a time- and dose-dependent increase in the number of cellular insulin receptors (Knutson, V. P., Ronnett, G. V., and Lane, M. D. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 2822-2826). Cellular events relating to the insulin receptor and insulin responsiveness which occur over the time course of the transition to the "up-regulated" steady state are described. Over the 48-h transition from the basal to the up-regulated steady state, a transient increase in the level of intracellular receptor was detected with a 3-5-fold increase in intracellular receptor found 12 h after steroid administration. Through the use of the heavy isotope density shift, this increase in the intracellular receptor population was preceded by a decrease in the rate of receptor inactivation, with no change in receptor synthesis. Insulin-induced receptor down-regulation was abolished after 12 h of dexamethasone treatment, when the intracellular receptor level was elevated. Nevertheless, the cells maintained the ability to internalize receptor in response to insulin binding. The hormonal responsiveness of the cells over the glucocorticoid-induced transition was assessed by the ability of insulin to stimulate the cellular uptake of 2-deoxyglucose and aminoisobutyric acid. Glucose transport was transiently increased at a time when the intracellular population of receptor was transiently elevated. Glucocorticoid treatment ultimately led to a loss of insulin-sensitive glucose transport. Insulin-stimulated amino acid transport was transiently abolished when the intracellular population of receptor was high. With chronic steroid treatment, the sensitivity of the amino acid transporter was increased above control levels. These data would indicate that glucocorticoids have no short- or long-term effect on insulin receptor synthesis; the insulin-induced internalization of insulin receptor alone is not sufficient to induce a cellular response to insulin; and the cellular events leading to the transient accumulation of intracellular receptor are coupled to the cellular responsiveness of the cells to insulin.
已证明用糖皮质激素处理汇合的胚胎瑞士小鼠成纤维细胞（3T3 - C2细胞）会导致细胞胰岛素受体数量呈时间和剂量依赖性增加（克努森，V. P.，罗内特，G. V.，和莱恩，M. D.（1982年）《美国国家科学院院刊》79，2822 - 2826）。描述了在向“上调”稳态转变的时间过程中发生的与胰岛素受体和胰岛素反应性相关的细胞事件。在从基础状态到上调稳态的48小时转变过程中，检测到细胞内受体水平短暂升高，在给予类固醇后12小时细胞内受体增加3 - 5倍。通过使用重同位素密度转移，细胞内受体群体的这种增加之前是受体失活速率的降低，而受体合成没有变化。地塞米松处理12小时后，当细胞内受体水平升高时，胰岛素诱导的受体下调被消除。然而，细胞仍保持响应胰岛素结合而内化受体的能力。通过胰岛素刺激细胞摄取2 - 脱氧葡萄糖和氨基异丁酸的能力来评估细胞在糖皮质激素诱导的转变过程中的激素反应性。当细胞内受体群体短暂升高时，葡萄糖转运短暂增加。糖皮质激素处理最终导致胰岛素敏感的葡萄糖转运丧失。当细胞内受体群体较高时，胰岛素刺激的氨基酸转运短暂被消除。长期使用类固醇处理后，氨基酸转运体的敏感性增加到高于对照水平。这些数据表明糖皮质激素对胰岛素受体合成无短期或长期影响；仅胰岛素诱导的胰岛素受体内化不足以诱导细胞对胰岛素的反应；导致细胞内受体短暂积累的细胞事件与细胞对胰岛素的反应性相关。
