The beta(3)-adrenergic receptor inhibits insulin-stimulated leptin secretion from isolated rat adipocytes
The beta(3)-adrenergic receptor inhibits insulin-stimulated leptin secretion from isolated rat adipocytes
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DOI：
10.1210/en.137.9.4054
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发表时间：
1996-09-01
期刊：
影响因子：
4.8
通讯作者：
Watson, PM
中科院分区：
文献类型：
--
作者：
Gettys, TW;Harkness, PJ;Watson, PM
各种模型系统已被用来研究最近克隆的 ob 基因瘦素的表达。在这里，我们报道了新鲜分离的大鼠白色脂肪细胞与胰岛素一起孵育，以快速且浓度依赖性的方式释放瘦素（EC（50）为0.221 +/- .075 nM）。胰岛素刺激的瘦素释放最早可在 30 分钟内检测到，10 nM 胰岛素可产生最大 2-3 倍的效果。同时激活 cAMP 依赖性蛋白激酶可完全阻断胰岛素的作用。使用脂解的激活作为 cAMP 依赖性蛋白激酶活性的指标，我们发现去甲肾上腺素或选择性 β(3)-肾上腺素受体激动剂 CL316,243 对瘦素释放的抑制与 cAMP 依赖性蛋白激酶的激活同时发生。此外，β(1)-和β(2)-肾上腺素能受体拮抗剂不会损害去甲肾上腺素或CL316,243抑制脂肪细胞释放瘦素的能力。这些发现表明，β(3)-肾上腺素能受体在调节脂肪细胞瘦素的释放中发挥着核心作用。
Various model systems have been used to study the expression of the recently cloned ob gene, leptin. Here we report that freshly isolated rat white adipocytes incubated with insulin release leptin in a rapid and concentration-dependent manner (EC(50) of 0.221 +/- .075 nM). Insulin-stimulated leptin release could be detected as early as 30 min and a maximal 2-3 fold effect was produced by 10 nM insulin, The effect of insulin was completely blocked by simultaneous activation of cAMP-dependent protein kinase. Using the activation of lipolysis as an index of cAMP-dependent protein kinase activity, we show that inhibition of leptin release by norepinephrine or the selective beta(3)-adrenergic receptor agonist, CL316,243, occurred in parallel to activation of cAMP-dependent protein kinase. In addition, beta(1)- and beta(2)-adrenergic receptor antagonists did not impair the ability of norepinephrine or CL316,243 to inhibit leptin release from the adipocytes. These findings suggest that the beta(3)-adrenergic receptor plays a central role in regulating the release of leptin from the adipocyte.