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Insulin induces alpha(1B)-adrenergic receptor phosphorylation and desensitization

机译:胰岛素诱导α(1B)-肾上腺素能受体磷酸化和脱敏

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The ability of insulin to induce alpha(1B)-adrenoceptor phosphorylation and desensitization was tested in two model systems: rat-1 cells that stably express alpha(1B)-adrenoceptors, through transfection, and endogenously express insulin receptors and DDT1 MF2 cells that endogenously express both receptors. Insulin induced concentration-dependent increases in the phosphorylation state of the adrenergic receptors in the two models with similar EC50 values (0.5-2 nM). The effect was rapid in the two systems but it was sustained in rat-1 cells and transient in DDT1 MF2 cells. In both cell lines, the insulin-mediated phosphorylation of alpha(1B)-adrenoceptors was blocked by wortmannin and LY 294002, and by staurosporine and bisindolylmaleimide I, indicating that the effect involved phosphoinositide 3-kinase and protein kinase C activities. The adrenoceptor phosphorylation induced by insulin was associated to desensitization as evidences by a diminished elevation of intracellular calcium in response to noradrenaline. Inhibitors of phosphoinositide 3-kinase and protein kinase C blocked the functional desensitization induced by insulin. (C) 2004 Elsevier Inc. All rights reserved.
机译:在两个模型系统中测试了胰岛素诱导α(1B)-肾上腺素受体磷酸化和脱敏的能力:通过转染稳定表达α(1B)-肾上腺素受体的大鼠1细胞,以及内源性表达内源性胰岛素受体和DDT1 MF2细胞表达两种受体。在两个具有相似EC50值(0.5-2 nM)的模型中,胰岛素引起肾上腺素能受体磷酸化状态的浓度依赖性增加。在两个系统中该作用迅速,但在大鼠1细胞中持续,在DDT1 MF2细胞中短暂。在这两种细胞系中,胰岛素介导的α(1B)-肾上腺素受体的磷酸化被渥曼青霉素和LY 294002以及星形孢菌素和双吲哚基马来酰亚胺I阻断,表明该作用涉及磷酸肌醇3-激酶和蛋白激酶C的活性。胰岛素诱导的肾上腺素能受体磷酸化与脱敏有关,这是通过响应去甲肾上腺素降低细胞内钙的升高来证明的。磷酸肌醇3-激酶和蛋白激酶C的抑制剂阻断了胰岛素诱导的功能性脱敏。 (C)2004 Elsevier Inc.保留所有权利。

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